[1] Alzheimer A, Stelzmann RA , Schnitzlein HN , Murtagh FR (1995) An English translation of Alzheimer’s 1907 paper, “Über eine eigenartige Erkankung der Hirnrinde.”, Clin Anat 8, 429–431.
[2] DeTure MA , Dickson DW (2019) The neuropathological diagnosis of Alzheimer’s disease, Mol Neurodegener 14, 32.
[3] Suzuki K , Parker CC , Pentchev PG , Katz D , Ghetti B , D’Agostino AN , Carstea ED (1995) Neurofibrillary tangles in Niemann-Pick disease type C, Acta Neuropathol 89, 227–238.
[4] Malek-Ahmadi M , Chen K , Perez SE , Mufson EJ (2019) Cerebral amyloid angiopathy and neuritic plaque pathology correlate with cognitive decline in elderly non-demented individuals, J Alzheimers Dis 67, 411–422.
[5] Götz J , Ittner LM (2008) Animal models of Alzheimer’s disease and frontotemporal dementia, Nat Rev Neurosci 9, 532–544.
[6] OECD (2013) Dementia prevalence. In OECD, Health at a Glance 2013: OECD Indicators. OECD Publishing.
[7] Hardy J (2006) A hundred years of Alzheimer’s disease research, Neuron 52, 3–13.
[8] Castellani RJ , Perry G (2012) Pathogenesis and disease-modifying therapy in Alzheimer’s disease: The flat line of progress, Arch Med Res 43, 694–698.
[9] National Institute on Aging, How Is Alzheimer’s Disease Treated? https://www.nia.nih.gov/health/how-alzheimers-disease-treated
[10] Wallis C (2019) It’s time to shift tactics on Alzheimer’s disease, Sci Am 22, https://www.scientificamerican.com/article/its-time-to-shift-tactics-on-alzheimers-disease/.
[11] Contestabile A (2011) The history of the cholinergic hypothesis, Behav Brain Res 221, 334–340.
[12] Frölich L (2002) The cholinergic pathology in Alzheimer’s disease–discrepancies between clinical experience and pathophysiological findings, J Neural Transm (Vienna) 109, 1003–1013.
[13] Pimplikar SW (2009) Reassessing the amyloid cascade hypothesis of Alzheimer’s disease, Int J Biochem Cell Biol 41, 1261–1268.
[14] Wu L , Rosa-Neto P , Hsiung GY , Sadovnick AD , Masellis M , Black SE , Jia J , Gauthier S (2012) Early-onset familial Alzheimer’s disease (EOFAD), Can J Neurol Sci 39, 436–445.
[15] Nieuwenhuis-Mark RE (2009) Diagnosing Alzheimer’s dementia in Down syndrome: Problems and possible solutions, Res Dev Disabil 30, 827–838.
[16] Sweeney MD , Sagare AP , Zlokovic BV (2018) Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders, Nat Rev Neurol 14, 133–150.
[17] Lam FC , Liu R , Lu P , Shapiro AB , Renoir JM , Sharom FJ , Reiner PB (2001) β-Amyloid efflux mediated by p-glycoprotein, J Neurochem 76, 1121–1128.
[18] Ma Q , Zhao Z , Sagare AP , Wu Y , Wang M , Owens NC , Verghese PB , Herz J , Holtzman DM , Zlokovic BV (2018) Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism, Mol Neurodegener 13, 57.
[19] Wei W , Bodles-Brakhop AM , Barger SW (2016) A role for P-glycoprotein in clearance of Alzheimer amyloid β-peptide from the brain, Curr Alzheimer Res 13, 615–620.
[20] Zhao Z , Sagare AP , Ma Q , Halliday MR , Kong P , Kisler K , Winkler EA , Ramanathan A , Kanekiyo T , Bu G , Owens NC , Rege SV , Si G , Ahuja A , Zhu D , Miller CA , Schneider JA , Maeda M , Maeda T , Sugawara T , Ichida JK , Zlokovic BV (2015) Central role for PICALM in amyloid–β blood–brain barrier transcytosis and clearance, Nat Neurosci 18, 978–987.
[21] Miller MC , Tavares R , Johanson CE , Hovanesian V , Donahue JE , Gonzalez L , Silverberg GD , Stopa EG (2008) Hippocampal RAGE immunoreactivity in early and advanced Alzheimer’s disease, Brain Res 1230, 273–280.
[22] Liu CC , Liu CC , KanekiyoT , Xu H , Bu G (2013) Apolipoprotein E and Alzheimer disease: Risk, mechanisms, and therapy, Nat Rev Neurol 9, 106–118.
[23] Deane R , Sagare A , Hamm K , Parisi M , Lane S , Finn MB , Holtzman DM , Zlokovic BV (2008) apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain, J Clin Invest 118, 4002–4013.
[24] Kivipelto M , Laakso MP , Tuomilehto J , Nissinen A , Soininen H (2002) Hypertension and hypercholesterolaemia as risk factors for Alzheimer’s disease: Potential for pharmacological intervention, CNS Drugs 16, 435–444.
[25] Whitmer RA , Gunderson EP , Barrett-Connor E , Quesenberry CP , Yaffe K (2005) Obesity in middle age and future risk of dementia: A 27 year longitudinal population based study, BMJ 330, 1360.
[26] Kivipelto M , Ngandu T , Fratiglioni L , Viitanen M , Kåreholt I , Winblad B , Helkala EL , Tuomilehto J , Soininen H , Nissinen A (2005) Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease, Arch Neurol 62, 1556–1560.
[27] Rhea EM , Salameh TS , Logsdon AF , Hanson AJ , Erickson MA , Banks WA (2017) Blood-brain barriers in obesity, AAPS J 19, 921–930.
[28] Jayaraj RL , Azimullah S , Beiram R (2020) Diabetes as a risk factor for Alzheimer’s disease in the Middle East and its shared pathological mediators, Saudi J Biol Sci 27, 736–750.
[29] Durazzo TC , Mattsson N , Weiner MW ; Alzheimer’s Disease Neuroimaging Initiative (2014) Smoking and increased Alzheimer’s disease risk: A review of potential mechanisms, Alzheimers Dement 10, S122–S145.
[30] Justice NJ (2018) The relationship between stress and Alzheimer’s disease, Neurobiol Stress 8, 127–133.
[31] Macedo AC , Balouch S , Tabet N (2017) Is sleep disruption a risk factor for Alzheimer’s disease? J Alzheimer Dis 58, 993–1002.
[32] Gottlieb S (2000) Head injury doubles the risk of Alzheimer’s disease, BMJ 321, 1100.
[33] Guerreiro R , Bras J (2015) The age factor in Alzheimer’s disease, Genome Med 7, 106.
[34] Unnithan AKA , Mehta P (2021) Hemorrhagic stroke. In StatPearls, StatPearls Publishing, Treasure Island (FL).
[35] Cohn JN (1995) Structural changes in cardiovascular disease, Am J Cardiol 76, 34E–37E.
[36] Osterhoff G , Morgan EF , Shefelbine SJ , Karim L , McNamara LM , Augat P (2016) Bone mechanical properties and changes with osteoporosis, Injury 47(Suppl 2), S11–S20.
[37] Michael R , Bron AJ (2011) The ageing lens and cataract: A model of normal and pathological ageing, Philos Trans R Soc Lond B Biol Sci 366, 1278–1292.
[38] Bonilha VL (2008) Age and disease-related structural changes in the retinal pigment epithelium, Clin Ophthalmol 2, 413–424.
[39] Paplou V , Schubert NMA , Pyott SJ (2021) Age-related changes in the cochlea and vestibule: Shared patterns and processes, Front Neurosci 15, 680856.
[40] Cox LG , van Rietbergen B , van Donkelaar CC , Ito K (2011) Bone structural changes in osteoarthritis as a result of mechanoregulated bone adaptation: A modeling approach, Osteoarthritis Cartilage 19, 676–682.
[41] Li Y , Roberts ND , Wala JA , Shapira O , Schumacher SE , Kumar K , Khurana E , Waszak S , Korbel JO , Haber JE , Imielinski M ; PCAWG Structural Variation Working Group, Weischenfeldt J , Beroukhim R , Campbell PJ ; PCAWG Consortium (2020) Patterns of somatic structural variation in human cancer genomes, Nature 578, 112–121.
[42] Iadecola C , Gorelick PB (2003) Converging pathogenic mechanisms in vascular and neurodegenerative dementia, Stroke 34, 335–337.
[43] Ujiie M , Dickstein DL , Carlow DA , Jefferies WA (2003) Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model, Microcirculation 10, 463–470.
[44] Dickstein DL , Biron KE , Ujiie M , Pfeifer CG , Jeffries AR , Jefferies WA (2006) Abeta peptide immunization restores blood-brain barrier integrity in Alzheimer disease, FASEB J 20, 426–433.
[45] Popescu BO , Toescu EC , Popescu LM , Bajenaru O , Muresanu DF , Schultzberg M , Bogdanovic N (2009) Blood-brain barrier alterations in ageing and dementia, J Neurol Sci 283, 99–106.
[46] Kook SY , Hong HS , Moon M , Ha CM , Chang S , Mook-Jung I (2012) Aβ1–42-RAGE interaction disrupts tight junctions of the blood–brain barrier via Ca2+-Calcineurin signaling, J Neurosci 32, 8845–8854.
[47] Montagne A , Zhao Z , Zlokovic BV (2017) Alzheimer’s disease: A matter of blood–brain barrier dysfunction? J Exp Med 214, 3151–3169.
[48] Paul J , Strickland S , Melchor JP (2007) Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer’s disease, J Exp Med 204, 1999–2008.
[49] Cortes-Canteli M , Strickland S (2009) Fibrinogen, a possible key player in Alzheimer’s disease, J Thromb Haemost 7(Suppl 1), 146–150.
[50] Saunders NR , Dziegielewska KM , Møllgård K , Habgood MD (2015) Markers for blood-brain barrier integrity: How appropriate is Evans blue in the twenty-first century and what are the alternatives? Front Neurosci 9, 385.
[51] Marchi N , Cavaglia M , Fazio V , Bhudia S , Hallene K , Janigro D (2004) Peripheral markers of blood-brain barrier damage, Clin Chim Acta 342, 1–12.
[52] Takechi R , Galloway S , Pallebage-Gamarallage MM , Wellington CL , Johnsen RD , Dhaliwal SS , Mamo JC (2010) Differential effects of dietary fatty acids on the cerebral distribution of plasma-derived apo B lipoproteins with amyloid-β, Br J Nutr 103, 652–662.
[53] Stein TD , Alvarez VE , McKee AC (2014) Chronic traumatic encephalopathy: A spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel, Alzheimers Res Ther 6, 4.
[54] Chodobski A , Zink BJ , Szmydynger-Chodobska J (2011) Blood–brain barrier pathophysiology in traumatic brain injury, Transl Stroke Res 2, 492–516.
[55] Doherty CP , O’Keefe E , Wallace E , Loftus T , Keaney J , Kealy J , Humphries MM , Molloy MG , Meaney JF , Farrell M , Campbell M (2016) Blood–brain barrier dysfunction as a hallmark pathology in chronic traumatic encephalopathy, J Neuropathol Exp Neurol 75, 656–662.
[56] Johnson VE , Weber MT , Xiao R , Cullen DK , Meaney DF , Stewart W , Smith DH (2018) Mechanical disruption of the blood–brain barrier following experimental concussion, Acta Neuropathol 135, 711–726.
[57] Farrell M , Aherne S , O’Riordan S , O’Keeffe E , Greene C , Campbell M (2019) Blood-brain barrier dysfunction in a boxer with chronic traumatic encephalopathy and schizophrenia, Clin Neuropathol 38, 51–58.
[58] Salloway S , Gur T , Berzin T , Tavares R , Zipser B , Correia S , Hovanesian V , Fallon J , Kuo-Leblanc V , Glass D , Hulette C , Rosenberg C , Vitek M , Stopa E (2002) Effect of APOE genotype on microvascular basement membrane in Alzheimer’s disease, J Neurol Sci 203-204, 183–187.
[59] Mazzone P , Tierney W , Hossain M , Puvenna V , Janigro D , Cucullo L (2010) Pathophysiological impact of cigarette smoke exposure on the cerebrovascular system with a focus on the blood-brain barrier: Expanding the awareness of smoking toxicity in an underappreciated area, Int J Environ Res Public Health 7, 4111–4126.
[60] Prasad S , Sajja RK , Naik P , Cucullo L (2014) Diabetes mellitus and blood-brain barrier dysfunction: An overview, J Pharmacovigil 2, 125.
[61] Alluri H , Wiggins-Dohlvik K , Davis ML , Huang JH , Tharakan B (2015) Blood-brain barrier dysfunction following traumatic brain injury, Metab Brain Dis 30, 1093–1104.
[62] Girouard H (2016) Hypertension and the Brain as an End-Organ Target, Springer.
[63] Montagne A , Nation DA , Sagare AP , Barisano G , Sweeney MD , Chakhoyan A , Pachicano M , Joe E , Nelson AR , D’Orazio LM , Buennagel DP , Harrington MG , Benzinger TLS , Fagan AM , Ringman JM , Schneider LS , Morris JC , Reiman EM , Caselli RJ , Chui HC , Tcw J , Chen Y , Pa J , Conti PS , Law M , Toga AW , Zlokovic BV (2020) APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline, Nature 581, 71–76.
[64] Hurtado-Alvarado G , Velázquez-Moctezuma J , Gómez-González B (2017) Chronic sleep restriction disruptsinterendothelial junctions in the hippocampus and increasesblood–brain barrier permeability, J Microsc 268, 28–38.
[65] Dudek KA , Dion-Albert L , Lebel M , LeClair K , Labrecque S , Tuck E , Perez CF , Golden SA , Tamminga C , Turecki G , Mechawar N , Russo SJ , Menard C (2020) Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression, Proc Natl Acad Sci U S A 117, 3326–3336.
[66] Welcome MO , Mastorakis NE (2020) Stress-induced blood brain barrier disruption: Molecular mechanisms and signaling pathways, Pharmacol Res 157, 104769.
[67] Sohrabji F (2018) Guarding the blood–brain barrier: A role for estrogen in the etiology of neurodegenerative disease, Gene Expr 13, 311–319.
[68] Ahmadpour D , Grange-Messent V (2021) Involvement of testosterone signaling in the integrity of the neurovascular unit in the male: Review of evidence, contradictions, and hypothesis, Neuroendocrinology 111, 403–420.
[69] Jancsó G , Domoki F , Sántha P , Varga J , Fischer J , Orosz K , Penke B , Becskei A , Dux M , Tóth L (1998) Beta-amyloid (1-42)peptide impairs blood-brain barrier function after intracarotidinfusion in rats, Neurosci Lett 253, 139–141.
[70] Farkas IG , Czigner A , Farkas E , Dobó E , Soós K , Penke B , Endrész V , Mihály A (2003) Beta-amyloid peptide-inducedblood-brain barrier disruption facilitates T-cell entry into the ratbrain, Acta Histochem 105, 115–125.
[71] Tai LM , Holloway KA , Male DK , Loughlin AJ , Romero IA (2010) Amyloid-β-induced occludin down-regulation and increased permeability in human brain endothelial cells is mediated by MAPK activation, J Cell Mol Med 14, 1101–1112.
[72] Gosselet F , Saint-Pol J , Candela P , Fenart L (2013) Amyloid-β peptides, Alzheimer’s disease and the blood-brain barrier, Curr Alzheimer Res 10, 1015–1033.
[73] Ohtsuki S , Sato S , Yamaguchi H , Kamoi M , Asashima T , Terasaki T (2007) Exogenous expression of claudin-5 induces barrier properties in cultured rat brain capillary endothelial cells, J Cell Physiol 210, 81–86.
[74] Hartz AM , Bauer B , Soldner EL , Wolf A , Boy S , Backhaus R , Mihaljevic I , Bogdahn U , Klünemann HH , Schuierer G , Schlachetzki F (2012) Amyloid-β contributes to blood–brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy, Stroke 43, 514–523.
[75] Marco S , Skaper SD (2006) Amyloid β-peptide1–42 alters tight junction protein distribution and expression in brain microvessel endothelial cells, Neurosci Lett 401, 219–224.
[76] Carrano A , Hoozemans JJ , van der Vies SM , Rozemuller AJ , van Horssen J , de Vries HE (2011) Amyloid Beta induces oxidative stress-mediated blood-brain barrier changes in capillary amyloid angiopathy, Antioxid Redox Signal 15, 1167–1178.
[77] Lee JM , Yin K , Hsin I , Chen S , Fryer JD , Holtzman DM , Hsu CY , Xu J (2005) Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage, J Neurol Sci 229-230, 249–254.
[78] Brkic M , Balusu S , Wonterghem EV , Gorlé N , Benilova I , Kremer A , Hove IV , Moons L , Strooper BD , Kanazir S , Libert C , Vandenbroucke RE (2015) Amyloid β oligomers disrupt blood–CSF barrierintegrity by activating matrix metalloproteinases, J Neurosci 35, 12766–12778.
[79] Thomas T , McLendon C , Sutton ET , Thomas G (1997) Cerebrovascular endothelial dysfunction mediated by beta-amyloid, Neuroreport 8, 1387–1391.
[80] Blanc EM , Toborek M , Mark RJ , Hennig B , Mattson MP (1997) Amyloid beta-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells, J Neurochem 68, 1870–1881.
[81] Fossati S , Ghiso J , Rostagno A (2012) Insights into caspase-mediated apoptotic pathways induced by amyloid-β in cerebral microvascular endothelial cells, Neurodegener Dis 10, 324–328.
[82] Biron KE , Dickstein DL , Gopaul R , Jefferies WA (2011) Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer’s disease, PLoS One 6, e23789.
[83] Magaki S , Tang Z , Tung S , Williams CK , Lo D , Yong WH , Khanlou N , Vinters HV (2018) The effects of cerebral amyloid angiopathy on integrity of the blood-brain barrier, Neurobiol Aging 70, 70–77.
[84] Viswanathan A , Greenberg SM (2011) Cerebral amyloid angiopathy in the elderly, Ann Neurol 70, 871–880.
[85] Ghiso J , Tomidokoro Y , Revesz T , Frangione B , Rostagno A (2010) Cerebral amyloid angiopathy and Alzheimer’s disease, Hirosaki Igaku 61, S111–S124.
[86] Bergeron C , Ranalli PJ , Miceli PN (1987) Amyloid angiopathy in Alzheimer’s disease, Can J Neurol Sci 14, 564–569.
[87] Thal DR , Griffin WS , de Vos RA , Ghebremedhin E (2008) Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease, Acta Neuropathol 115, 599–609.
[88] Pallebage-Gamarallage MM , Takechi R , Lam V , Galloway S , Dhaliwal S , Mamo JC (2010) Post-prandial lipid metabolism, lipid-modulating agents and cerebrovascular integrity: Implications for dementia risk, Atheroscler Suppl 11, 49–54.
[89] Mamo JC , Jian L , James AP , Flicker L , Esselmann H , Wiltfang J (2008) Plasma lipoprotein beta-amyloid in subjects with Alzheimer’s disease or mild cognitive impairment, Ann Clin Biochem 45, 395–403.
[90] Galloway S , Takechi R , Pallebage-Gamarallage MM , Dhaliwal SS , Mamo JC (2009) Amyloid-β colocalizes with apolipoprotein B in absorptive cells of the small intestine, Lipids Health Dis 8, 46.
[91] Foley P (2010) Lipids in Alzheimer’s disease: A century-old story, Biochim Biophys Acta 1801, 750–753.
[92] LIPID MAPS® Lipidomics Gateway.
[93] Galloway S , Jian L , Johnsen R , Chew S , Mamo JCL (2007) [beta]-Amyloid or its precursor protein is found in epithelial cells of the small intestine and is stimulated by high-fat feeding, J Nutr Biochem 18, 279–284.
[94] Takechi R , Galloway S , Pallebage-Gamarallage MM , Mamo JC (2008) Chylomicron amyloid-beta in the aetiology of Alzheimer’s disease, Atheroscler Suppl 9, 19–25.
[95] Gosselet F (2011) The mysterious link between cholesterol andAlzheimer’s disease: Is the blood-brain barrier a suspect? JAlzheimers Dis Parkinsonism 1, 103e.
[96] Lambert JC , Heath S , Even G , Campion D , Sleegers K , Hiltunen M , Combarros O , Zelenika D , Bullido MJ , Tavernier B , Letenneur L , Bettens K , Berr C , Pasquier F , Fiévet N , Barberger-Gateau P , Engelborghs S , De Deyn P , Mateo I , Franck A , Helisalmi S , Porcellini E , Hanon O ; European Alzheimer’s Disease Initiative Investigators, de Pancorbo MM , Lendon C , Dufouil C , Jaillard C , Leveillard T , Alvarez V , Bosco P , Mancuso M , Panza F , Nacmias B , Bossù P , Piccardi P , Annoni G , Seripa D , Galimberti D , Hannequin D , Licastro F , Soininen H , Ritchie K , Blanché H , Dartigues JF , Tzourio C , Gut I , Van Broeckhoven C , Alpérovitch A , Lathrop M , Amouyel P (2009) Genome-wide association study identifies variants at CLU andCR1 associated with Alzheimer’s disease, Nat Genet 41, 1094–1099.
[97] Hollingworth P , Harold D , Sims R , Gerrish A , Lambert JC , Carrasquillo MM , Abraham R , Hamshere ML , Pahwa JS , Moskvina V , et al. (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease, Nat Genet 43, 429–435.
[98] Bereczki E , Bernát G , Csont T , Ferdinandy P , Scheich H , Sántha M (2008) Overexpression of human Apolipoprotein B-100induces severe neurodegeneration in transgenic mice, J ProteomeRes 7, 2246–2252.
[99] Caramelli P , Nitrini R , Maranhão R , Lourenço ACG , Damasceno MC , Vinagre C , Caramelli B (1999) Increased apolipoprotein B serum concentration in Alzheimer’s disease, Acta Neurol Scand 100, 61–63.
[100] Solomon A , Kivipelto M , Wolozin B , Zhou J , Whitmer RA (2009) Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later, Dement Geriatr Cogn Disord 28, 75–80.
[101] Nicholson AM , Ferreira A (2010) Cholesterol and neuronal susceptibility to beta-amyloid toxicity, Cogn Sci (Hauppauge) 5, 35–56.
[102] Xiong H , Callaghan D , Jones A , Walker DG , Lue LF , Beach TG , Sue LI , Woulfe J , Xu H , Stanimirovic DB , Zhang W (2008) Cholesterol retention in Alzheimer’s brain is responsible for high β- and γ-secretase activities and Aβ production, Neurobiol Dis 29, 422–437.
[103] Kiskis J , Fink H , Nyberg L , Thyr J , Li JY , Enejder A (2015) Plaque-associated lipids in Alzheimer’s diseased brain tissue visualized by nonlinear microscopy, Sci Rep 5, 13489.
[104] Mori T , Paris D , Town T , Rojiani AM , Sparks DL , Delledonne A , Crawford F , Abdullah LI , Humphrey JA , Dickson DW , Mullan MJ (2001) Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APPsw mice, J Neuropathol Exp Neurol 60, 778–785.
[105] Saito Y , Suzuki K , Nanba E , Yamamoto T , Ohno K , Murayama S (2002) Niemann-Pick type C disease: Accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity, Ann Neurol 52, 351–355.
[106] Distl R , Treiber-Held S , Albert F , Meske V , Harzer K , Ohm TG (2003) Cholesterol storage and tau pathology in Niemann-Pick type C disease in the brain, J Pathol 200, 104–111.
[107] Bowman GL , Quinn JF (2008) Alzheimer’s disease and the blood-brain barrier: Past, present and future, Aging Health 4, 47–55.
[108] Skillbäck T , Delsing L , Synnergren J , Mattsson N , Janelidze S , Nägga K , Kilander L , Hicks R , Wimo A , Winblad B , Hansson O , Blennow K , Eriksdotter M , Zetterberg H (2017) CSF/serum albumin ratio in dementias: A cross-sectional study on 1861 patients, Neurobiol Aging 59, 1–9.
[109] Sweeney MD , Sagare AP , Zlokovic BV (2015) Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer’s disease, J Cereb Blood Flow Metab 35, 1055–1068.
[110] Namba Y , Tsuchiya H , Ikeda K (1992) Apolipoprotein B immunoreactivity in senile plaque and vascular amyloids and neurofibrillary tangles in the brains of patients with Alzheimer’s disease, Neurosci Lett 134, 264–266.
[111] Takechi R , Galloway S , Pallebage-Gamarallage M , Wellington C , Johnsen R , Mamo JC (2009) Three-dimensional colocalization analysis of plasma-derived apolipoprotein B with amyloid plaques in APP/PS1 transgenic mice, Histochem Cell Biol 131, 661–666.
[112] Lam V , Takechi R , Pallebage-Gamarallage MM , Galloway S , Mamo JC (2011) Colocalisation of plasma derived apo B lipoproteins with cerebral proteoglycans in a transgenic-amyloid model of Alzheimer’s disease, Neurosci Lett 492, 160–164.
[113] Banks WA (2006) The dam breaks: Disruption of the blood-brain barrier in diabetes mellitus, Am J Physiol Heart Circ Physiol 291, H2595–H2596.
[114] van der Vusse GJ (2009) Albumin as fatty acid transporter, Drug Metab Pharmacokinet 24, 300–307.
[115] Young SG (1990) Recent progress in understanding apolipoprotein B, Circulation 82, 1574–1594.
[116] Takechi R , Galloway S , Pallebage-Gamarallage MM , Lam V , Dhaliwal SS , Mamo JC (2013) Probucol prevents blood–brain barrier dysfunction in wild-type mice induced by saturated fat or cholesterol feeding, Clin Exp Pharmacol Physiol 40, 45–52.
[117] Elliott DA , Weickert CS , Garner B (2010) Apolipoproteins in the brain: Implications for neurological and psychiatric disorders. Clin Lipidol 51, 555–573.
[118] Wang H , Eckel RH (2014) What are lipoproteins doing in the brain? Trends Endocrinol Metab 25, 8–14.
[119] Picard C , Nilsson N , Labonté A , Auld D , Rosa-Neto P ; Alzheimer’s Disease Neuroimaging Initiative, Ashton NJ , Zetterberg H , Blennow K , Breitner JCB , Villeneuve S , Poirier J ; PREVENT-AD research group (2021) Apolipoprotein B is a novel marker for early tau pathology inAlzheimer’s disease, Alzheimers Dement, doi: 10.1002/alz.12442
[120] Quehenberger O , Dennis EA (2011) The human plasma lipidome, N Engl J Med 365, 1812–1823.
[121] Jeske DJ , Dietschy JM (1980) Regulation of rates of cholesterol synthesis in vivo in the liver and carcass of the rat measured using [3H]water, J Lipid Res 21, 364–376.
[122] Dietschy JM , Turley SD (2004) Cholesterol metabolism in the central nervous system during early development and in the mature animal, J Lipid Res 45, 1375–1397.
[123] Hamilton J , Brunaldi K (2007) A model for fatty acid transport into the brain, J Mol Neurosci 33, 12–17.
[124] Zhang J , Liu Q (2015) Cholesterol metabolism and homeostasis in the brain, Protein Cell 6, 254–264.
[125] Feingold KR , Grunfeld C (2000) Introduction to lipids and lipoproteins. In Endotext, FeingoldKR, AnawaltB, BoyceA, ChrousosG, DunganK, GrossmanA, HershmanJM, KaltsasG, KochC, KoppP, KorbonitsM, McLachlanR, MorleyJE, NewM, PerreaultL, PurnellJ, RebarR, SingerF, TrenceDL, VinikA, WilsonDP, eds. MDText.com, Inc., South Dartmouth (MA).
[126] Bruce KD , Zsombok A , Eckel RH (2017) Lipid processing in the brain: A key regulator of systemic metabolism. Front Endocrinol (Lausanne) 8, 60.
[127] Vance DE , Vance JE (2008), Biochemistry of lipids, lipoproteins, and membranes, Elsevier.
[128] Ioannou MS , Jackson J , Sheu SH , Chang CL , Weigel AV , Liu H , Pasolli HA , Xu CS , Pang S , Matthies D , Hess HF , Lippincott-Schwartz J , Liu Z (2019) Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity, Cell 177, 1522–1535.e14.
[129] Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease, Free Radic Biol Med 23, 134–147.
[130] Hensley K (2010) Neuroinflammation in Alzheimer’s disease: Mechanisms, pathologic consequences, and potential for therapeutic manipulation, J Alzheimers Dis 21, 1–14.
[131] Moreno-Jiménez EP , Flor-García M , Terreros-Roncal J , Rábano A , Cafini F , Pallas-Bazarra N , Ávila J , Llorens-Martín M (2019) Adult hippocampal neurogenesis isabundant in neurologically healthy subjects and drops sharply inpatients with Alzheimer’s disease, Nat Med 25, 554–560.
[132] Simons M , Keller P , Dichgans J , Schulz JB (2001) Cholesterol and Alzheimer’s disease: Is there a link? Neurology 57, 1089–1093.
[133] Wolozin B (2004) Cholesterol and the biology of Alzheimer’s disease, Neuron 41, 7–10.
[134] Zenaro E , Piacentino G , Constantin G (2017) The blood-brain barrier in Alzheimer’s disease, Neurobiol Dis 107, 41–56.
[135] Montagne A , Barnes SR , Sweeney MD , Halliday MR , Sagare AP , Zhao Z , Toga AW , Jacobs RE , Liu CY , Amezcua L , Harrington MG , Chui HC , Law M , Zlokovic BV (2015) Blood-brain barrier breakdown in the aging human hippocampus, Neuron 85, 296–302.
[136] Di Paolo G , Kim TW (2011) Linking lipids to Alzheimer’s disease: Cholesterol and beyond, Nat Rev Neurosci 12, 284–296.
[137] Kao YC , Ho PC , Tu YK , Jou IM , Tsai KJ (2020) Lipids and Alzheimer’s disease, Int J Mol Sci 21, 1505.
[138] Takechi R , Galloway S , Pallebage-Gamarallage MM , Lam V , Mamo JC (2010) Dietary fats, cerebrovasculature integrity and Alzheimer’s disease risk, Prog Lipid Res 49, 159–170.
[139] Wiegmann C , Mick I , Brandl EJ , Heinz A , Gutwinski S (2020) Alcohol and dementia – what is the link? A systematic review, Neuropsychiatr Dis Treat 16, 87–99.
[140] Nixon K (2006) Alcohol and adult neurogenesis: Roles in neurodegeneration and recovery in chronic alcoholism, Hippocampus 16, 287–295.
[141] Morris SA , Eaves DW , Smith AR , Nixon K (2010) Alcohol inhibition of neurogenesis: A mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model, Hippocampus 20, 596–607.
[142] Nixon K , Crews FT (2002) Binge ethanol exposure decreases neurogenesis in adult rat hippocampus, J Neurochem 83, 1087–1093.
[143] Fadda F , Rossetti ZL (1998) Chronic ethanol consumption: From neuroadaptation to neurodegeneration, Prog Neurobiol 56, 385–431.
[144] Crews FT , Lawrimore CJ , Walter TJ , Coleman LG Jr (2017) The role of neuroimmune signaling in alcoholism, Neuropharmacology 122, 56–73.
[145] Crews FT (2008) Alcohol-related neurodegeneration and recovery, Alcohol Res Health 31, 377–388.
[146] Rang HP (2012) 23. Atherosclerosis and lipoprotein metabolism. In Rang & Dale’s pharmacology, Churchill Livingstone, Edinburgh.
[147] Brindley DN (1991) Chapter 6 Metabolism of triacylglycerols. In New Comprehensive Biochemistry, VanceDE, VanceJE, eds. Elsevier, pp. 171–203.
[148] Ahmadian M , E Duncan R , Jaworski K , Sarkadi-Nagy E , Sul HS (2007) Triacylglycerol metabolism in adipose tissue, Future Lipidol 2, 229–237.
[149] Beffert U , Danik M , Krzywkowski P , Ramassamy C , Berrada F , Poirier J (1998) The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer’s disease, Brain Res Brain Res Rev 27, 119–142.
[150] Björkhem I , Meaney S (2004) Brain cholesterol: Long secret life behind a barrier, Arterioscler Thromb Vasc Biol 24, 806–815.
[151] Orth M , Bellosta S (2012) Cholesterol: Its regulation and role in central nervous system disorders, Cholesterol 2012, 292598.
[152] Ballmer PE (2001) Causes and mechanisms of hypoalbuminaemia, Clin Nutr 20, 271–273.
[153] Schiff ER , Maddrey WC , Sorrell MF (2011) Chapter 2: Laboratory Tests. In Schiff’s Diseases of the Liver, John Wiley & Sons.
[154] Nag S (2003) Pathophysiology of blood-brain barrier breakdown. In The blood-brain barrier: Biology and research protocols, Humana Press, pp. 97.
[155] Banks WA (2008) Developing drugs that can cross the blood-brain barrier: Applications to Alzheimer’s disease, BMC Neurosci 9, S2.
[156] Schönfeld P , Reiser G (2013) Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain, J Cereb Blood Flow Metab 33, 1493–1499.
[157] Karmi A , Iozzo P , Viljanen A , Hirvonen J , Fielding BA , Virtanen K , Oikonen V , Kemppainen J , Viljanen T , Guiducci L , Haaparanta-Solin M , Någren K , Solin O , Nuutila P (2010) Increased brain fatty acid uptake in metabolic syndrome, Diabetes 59, 2171–2177.
[158] Panov A , Orynbayeva Z , Vavilin V , Lyakhovich V (2014) Fatty acids in energy metabolism of the central nervous system, Biomed Res Int 2014, 472459.
[159] Murphy EJ (2017) The blood–brain barrier and protein-mediated fatty acid uptake: Role of the blood–brain barrier as a metabolic barrier, J Neurochem 141, 324–329.
[160] Jha MK , Morrison BM (2018) Glia-neuron energy metabolism in health and diseases: New insights into the role of nervous system metabolic transporters, Exp Neurol 309, 23–31.
[161] Johnson RC , Young SK , Cotter R , Lin L , Rowe WB (1990) Medium-chain-triglyceride lipid emulsion: Metabolism and tissue distribution, Am J Clin Nutr 52, 502–508.
[162] Speijer D , Manjeri GR , Szklarczyk R (2014) How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation, Philos Trans R Soc Lond B Biol Sci 369, 20130446.
[163] Sokoloff L (1973) Metabolism of ketone bodies by the brain, Annu Rev Med 24, 271–280.
[164] Owen OE (2005) Ketone bodies as a fuel for the brain during starvation, Biochem Mol Biol Educ 33, 246–251.
[165] Yang H , Shan W , Zhu F , Wu J , Wang Q (2019) Ketone bodies in neurological diseases: Focus on neuroprotection and underlying mechanisms, Front Neurol 10, 585.
[166] Sultana R , Perluigi M , Butterfield DA (2013) Lipid peroxidation triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain, Free Radic Biol Med 62, 157–169.
[167] Olsson Y , Klatzo I , Sourander P , Steinwall O (1968) Blood-brain barrier to albumin in embryonic new born and adult rats, Acta Neuropathol 10, 117–122.
[168] Roheim PS , Carey M , Forte T , Vega GL (1979) Apolipoproteins in human cerebrospinal fluid, Proc Natl Acad Sci U S A 76, 4646–4649.
[169] Cipolla MJ (2009) Barriers of the CNS. In The Cerebral Circulation, Morgan & Claypool Life Sciences.
[170] Danik M , Champagne D , Petit-Turcotte C , Beffert U , Poirier J (1999) Brain lipoprotein metabolism and its relation to neurodegenerative disease, Crit Rev Neurobiol 13, 357–407.
[171] Ladu MJ , Reardon C , Eldik LV , Fagan AM , Bu G , Holtzman D , Getz GS (2000) Lipoproteins in the central nervous system, Ann N Y Acad Sci 903, 167–175.
[172] Mahley RW , Weisgraber KH , Huang Y (2006) Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease, Proc Natl Acad Sci U S A 103, 5644–5651.
[173] Farmer BC , Kluemper J , Johnson LA (2019) Apolipoprotein E4 alters astrocyte fatty acid metabolism and lipid droplet formation, Cells 8, 182.
[174] Pfrieger FW (2003) Outsourcing in the brain: Do neurons deend on cholesterol delivery by astrocytes? Bioessays 25, 72–78.
[175] Deoni SCL , Dean DC , O’Muircheartaigh J , Dirks H , Jerskey BA (2012) Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping, Neuroimage 63, 1038–1053.
[176] Lütjohann D , von Bergmann K (2003) 24S-hydroxycholesterol: A marker of brain cholesterol metabolism, Pharmacopsychiatry 36(Suppl 2), S102–S106.
[177] Kay AD , Day SP , Nicoll JA , Packard CJ , Caslake MJ (2003) Remodelling of cerebrospinal fluid lipoproteins after subarachnoid hemorrhage, Atherosclerosis 170, 141–146.
[178] Saunders N , Habgood M , Dziegielewska , Saunders N (1999) Barrier mechanisms in the brain, I. Adult brain, Clin Exp Pharmacol Physiol 26, 11–19.
[179] Pardridge WM , Mietus LJ (1980) Palmitate and cholesterol transport through the blood-brain barrier, J Neurochem 34, 463–466.
[180] Abbott NJ (2005) Dynamics of CNS barriers: Evolution, differentiation, and modulation, Cell Mol Neurobiol 25, 5–23.
[181] Bundgaard M , Abbott NJ (2008) All vertebrates started out with a glial blood-brain barrier 4-500 million years ago, Glia 56, 699–708.
[182] Bell RD , Winkler EA , Singh I , Sagare AP , Deane R , WU Z , Holtzman DM , Betsholtz C , Armulik A , Sallstrom J , Berk BC , Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A, Nature 485, 512–516.
[183] Salameh TS , Mortell WG , Logsdon AF , Butterfield DA , Banks WA (2019) Disruption of the hippocampal and hypothalamic blood–brain barrier in a diet-induced obese model of type II diabetes: Prevention and treatment by the mitochondrial carbonic anhydrase inhibitor, topiramate, Fluids Barriers CNS 16, 1.
[184] Pelisch N , Hosomi N , Ueno M , Nakano D , Hitomi H , Mogi M , Shimada K , Kobori H , Horiuchi M , Sakamoto H , Matsumoto M , Kohno M , Nishiyama A (2011) Blockade of AT1 receptors protects the blood–brain barrier and improves cognition in Dahl salt-sensitive hypertensive rats, Am J Hypertens 24, 362–368.
[185] Naik P , Cucullo L (2015) Pathobiology of tobacco smoking and neurovascular disorders: Untied strings and alternative products, Fluids Barriers CNS 12, 25.
[186] Hurtado-Alvarado G , Domínguez-Salazar E , Pavon L , Velázquez-Moctezuma J , Gómez-González B (2016) Blood-brain barrier disruption induced by chronic sleep loss:Low-grade inflammation may be the link, J Immunol Res 2016, e4576012.
[187] Abrahamson EE , Ikonomovic MD (2020) Brain injury-induced dysfunction of the blood brain barrier as a risk for dementia, Exp Neurol 328, 113257.
[188] Weber CM , Clyne AM (2021) Sex differences in the blood–brain barrier and neurodegenerative diseases, APL Bioeng 5, 011509.
[189] Venkat P , Chopp M , Chen J (2017) Blood–brain barrier disruption, vascular impairment, and ischemia/reperfusion damage in diabetic stroke, J Am Heart Assoc 6, e005819.
[190] Yamamoto M , Guo DH , Hernandez CM , Stranahan AM (2019) Endothelial Adora2a activation promotes blood–brain barrier breakdown and cognitive impairment in mice with diet-induced insulin resistance, J Neurosci 39, 4179–4192.
[191] Hossain M , Sathe T , Fazio V , Mazzone P , Weksler B , Janigro D , Rapp E , Cucullo L (2009) Tobacco smoke: A critical etiological factor for vascular impairment at the blood–brain barrier, Brain Res 1287, 192–205.
[192] Zielinski MR , Kim Y , Karpova SA , McCarley RW , Strecker RE , Gerashchenko D (2014) Chronic sleep restriction elevates brain Interleukin-1 beta and tumor necrosis factor-alpha and attenuates brain-derived neurotrophic factor expression, Neurosci Lett 580, 27–31.
[193] Pan W , Zadina JE , Harlan RE , Weber JT , Banks WA , Kastin AJ (1997) Tumor necrosis Factor-α: A neuromodulator in the CNS, Neurosci Biobehav Rev 21, 603–613.
[194] Wang Y , Jin S , Sonobe Y , Cheng Y , Horiuchi H , Parajuli B , Kawanokuchi J , Mizuno T , Takeuchi H , Suzumura A (2014) Interleukin-1β induces blood–brain barrier disruption by downregulating sonic hedgehog in astrocytes, PLoS One 9, e110024.
[195] Main BS , Villapol S , Sloley SS , Barton DJ , Parsadanian M , Agbaegbu C , Stefos K , McCann MS , Washington PM , Rodriguez OC , Burns MP (2018) Apolipoprotein E4 impairs spontaneous blood brain barrier repair following traumatic brain injury, Mol Neurodegener 13, 17.
[196] Jo DH , Kim JH , Heo JI , Kim JH , Cho CH (2013) Interaction between pericytes and endothelial cells leads to formation of tight junction in hyaloid vessels, Mol Cells 36, 465–471.
[197] Yang Y , Rosenberg GA (2011) Blood–brain barrier breakdown in acute and chronic cerebrovascular disease, Stroke 42, 3323–3328.
[198] Tagami M , Nara Y , Kubota A , Fujino H , Yamori Y (1990) Ultrastructural changes in cerebral pericytes and astrocytes of stroke-prone spontaneously hypertensive rats, Stroke 21, 1064–1071.
[199] Hurtado-Alvarado G , Cabañas-Morales AM , Gómez-Gónzalez B (2014) Pericytes: Brain-immune interface modulators, Front Integr Neurosci 7, 80.
[200] Patrick P , Price TO , Diogo AL , Sheibani N , Banks WA , Shah GN (2015) Topiramate protects pericytes from glucotoxicity: Role for mitochondrial CA VA in cerebromicrovascular disease in diabetes, J Endocrinol Diabetes 2, https://www.symbiosisonlinepublishing.com/endocrinology-diabetes/endocrinology-diabetes23.php.
[201] Winkler EA , Sagare AP , Zlokovic BV (2014) The pericyte: A forgotten cell type with important implications for Alzheimer’s disease? Brain Pathol 24, 371–386.
[202] Daneman R , Prat A (2015) The blood–brain barrier, Cold Spring Harb Perspect Biol 7, a020412.
[203] Argaw AT , Zhang Y , Snyder BJ , Zhao ML , Kopp N , Lee SC , Raine CS , Brosnan CF , John GR (2006) IL-1β regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program, J Immunol 177, 5574–5584.
[204] Viggars AP , Wharton SB , Simpson JE , Matthews FE , Brayne C , Savva GM , Garwood C , Drew D , Shaw PJ , Ince PG (2011) Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: A study in the MRC-CFAS population neuropathology cohort, Neurosci Lett 505, 25–30.
[205] Nair SA , Jagadeeshan S , Indu R , Sudhakaran PR , Pillai MR (2012) How intact is the basement membrane? Role of MMPs. In Biochemical Roles of Eukaryotic Cell Surface Macromolecules, SudhakaranPR, SuroliaA, eds. Springer, New York, NY, pp. 215–232.
[206] Dokken B (2008) The pathophysiology of cardiovascular disease and diabetes: Beyond blood pressure and lipids, Diabetes Spectr 21, 160–165.
[207] Thomsen MS , Routhe LJ , Moos T (2017) The vascular basement membrane in the healthy and pathological brain, J Cereb Blood Flow Metab 37, 3300–3317.
[208] Yang Y , Estrada EY , Thompson JF , Liu W , Rosenberg GA (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat, J Cereb Blood Flow Metab 27, 697–709.
[209] Pan W , Xiang S , Tu H , Kastin AJ (2006) Cytokines interact with the blood-brain barrier. In Blood-Brain Barriers, John Wiley & Sons, Ltd, pp. 247–264.
[210] Nation DA , Sweeney MD , Montagne A , Sagare AP , D’Orazio LM , Pachicano M , Sepehrband F , Nelson AR , Buennagel DP , Harrington MG , Benzinger TLS , Fagan AM , Ringman JM , Schneider LS , Morris JC , Chui HC , Law M , Toga AW , Zlokovic BV (2019) Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction, Nat Med 25, 270–276.
[211] Vanlandewijck M , He L , Mäe MA , Andrae J , Ando K , Del Gaudio F , Nahar K , Lebouvier T , Laviña B , Gouveia L , Sun Y , Raschperger E , Räsänen M , Zarb Y , Mochizuki N , Keller A , Lendahl U , Betsholtz C (2018) A molecular atlas of cell types and zonation in the brain vasculature, Nature 554, 475–480.
[212] Zhao L , Li Z , Vong JSL , Chen X , Lai HM , Yan LYC , Huang J , Sy SKH , Tian X , Huang Y , Chan HYE , So HC , Ng WL , Tang Y , Lin WJ , Mok VCT , Ko H (2020) Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain, Nat Commun 11, 4413.
[213] Koedam EL , Lauffer V , van der Vlies AE , van der Flier WM , Scheltens P , Pijnenburg YA (2010) Early-versus late-onset Alzheimer’s disease: More than age alone, J Alzheimers Dis 19, 1401–1408.
[214] Safieh M , Korczyn AD , Michaelson DM (2019) ApoE4: An emerging therapeutic target for Alzheimer’s disease, BMC Med 17, 64.
[215] Dorey E , Chang N , Liu QY , Yang Z , Zhang W (2014) Apolipoprotein E, amyloid-beta, and neuroinflammation in Alzheimer’s disease, Neurosci Bull 30, 317–330.
[216] Premkumar DR , Cohen DL , Hedera P , Friedland RP , Kalaria RN (1996) Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease, Am J Pathol 148, 2083–2095.
[217] Olichney JM , Hansen LA , Galasko D , Saitoh T , Hofstetter CR , Katzman R , Thal LJ (1996) The apolipoprotein E epsilon 4 allele is associated with increased neuritic plaques and cerebral amyloid angiopathy in Alzheimer’s disease and Lewy body variant, Neurology 47, 190–196.
[218] Alonzo NC , Hyman BT , Rebeck GW , Greenberg SM (1998) Progression of cerebral amyloid angiopathy: Accumulation of amyloid-beta40 in affected vessels, J Neuropathol Exp Neurol 57, 353–359.
[219] Fryer JD , Taylor JW , DeMattos RB , Bales KR , Paul SM , Parsadanian M , Holtzman DM (2003) Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice, J Neurosci 23, 7889–7896.
[220] Rannikmäe K , Kalaria RN , Greenberg SM , Chui HC , Schmitt FA , Samarasekera N , Al-Shahi Salman R , Sudlow CL (2014) APOE associations with severe CAA-associated vasculopathic changes – collaborative meta-analysis, J Neurol Neurosurg Psychiatry 85, 300–305.
[221] Dienel GA , Hertz L (2001) Glucose and lactate metabolism during brain activation, J Neurosci Res 66, 824–838.
[222] Demetrius LA , Magistretti PJ , Pellerin L (2015) Alzheimer’s disease: The amyloid hypothesis and the Inverse Warburg effect, Front Physiol 5, 522.
[223] Ding F , Yao J , Rettberg JR , Chen S , Brinton RD (2013) Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer’s mouse brain: Implication for bioenergetic intervention. PLoS One 8, e79977.
[224] Yao J , Rettberg JR , Klosinski LP , Cadenas E , Brinton RD (2011) Shift in brain metabolism in late onset Alzheimer’s disease: Implications for biomarkers and therapeutic interventions, Mol Aspects Med 32, 247–257.
[225] Bird MI , Munday LA , Saggerson ED , Clark JB (1985) Carnitine acyltransferase activities in rat brain mitochondria. Bimodal distribution, kinetic constants, regulation by malonyl-CoA and developmental pattern, Biochem J 226, 323–330.
[226] Yang SY , He XY , Schulz H (1987) Fatty acid oxidation in rat brain is limited by the low activity of 3-ketoacyl-coenzyme A thiolase, J Biol Chem 262, 13027–13032.
[227] Di Paola M , Lorusso M (2006) Interaction of free fatty acids with mitochondria: Coupling, uncoupling and permeability transition, Biochim Biophys Acta 1757, 1330–1337.
[228] Wojtczak L , Schönfeld P (1993) Effect of fatty acids on energy coupling processes in mitochondria, Biochim Biophys Acta 1183, 41–57.
[229] Schönfeld P , Wojtczak L (2008) Fatty acids as modulators of the cellular production of reactive oxygen species, Free Radic Biol Med 45, 231–241.
[230] Hoyer S , Nitsch R , Oesterreich K (1991) Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: A cross-sectional comparison against advanced late-onset and incipient early-onset cases, J Neural Transm Park Dis Dement Sect 3, 1–14.
[231] Costantini LC , Barr LJ , Vogel JL , Henderson ST (2008) Hypometabolism as a therapeutic target in Alzheimer’s disease, BMC Neurosci 9(Suppl 2), S16.
[232] Bojarski L , Herms J , Kuznicki J (2008) Calcium dysregulation in Alzheimer’s disease, Neurochem Int 52, 621–633.
[233] Kim J , Yang Y , Song SS , Na JH , Oh KJ , Jeong C , Yu YG , Shin YK (2014) Beta-amyloid oligomers activate apoptotic BAK pore for cytochrome c release, Biophys J 107, 1601–1608.
[234] Bartolucci M , Ravera S , Garbarino G , Ramoino P , Ferrando S , Calzia D , Candiani S , Morelli A , Panfoli I (2015) Functional expression of electron transport chain and FoF1-ATP synthase in optic nerve myelin sheath, Neurochem Res 40, 2230–2241.
[235] Ravera S , Bartolucci M , Cuccarolo P , Litamè E , Illarcio M , Calzia D , Degan P , Morelli A , Panfoli I (2015) Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability, Free Radic Res 49, 1156–1164.
[236] Papuć E , Rejdak K (2018) The role of myelin damage inAlzheimer’s disease pathology, Arch Med Sci 16, 345–351.
[237] Syapin PJ , Hickey WF (2006) Alcohol brain damage and neuroinflammation: Is there a connection? Alcohol Clin Exp Res 29, 1080–1089.
[238] Blanco AM , Guerri C (2007) Ethanol intake enhances inflammatory mediators in brain: Role of glial cells and TLR4/IL-1RI recetors. Front Biosci 12, 2616–2630.
[239] Crews FT , Nixon K (2009) Mechanisms of neurodegeneration and regeneration in alcoholism, Alcohol Alcohol 44, 115–127.
[240] Zhao YN , Wang F , Fan YX , Ping GF , Yang JY , Wu CF (2013) Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure, Behav Brain Res 236, 270–282.
[241] Walter TJ , Crews FT (2017) Microglial depletion alters the brain neuroimmune response to acute binge ethanol withdrawal, J Neuroinflammation 14, 86.
[242] Kaur G , Han SJ , Yang I , Crane C (2010) Microglia and central nervous system immunity, Neurosurg Clin N Am 21, 43–51.
[243] Yang I , Han SJ , Kaur G , Crane C , Parsa AT (2010) The role of microglia in central nervous system immunity and glioma immunology, J Clin Neurosci 17, 6–10.
[244] Gehrmann J , Matsumoto Y , Kreutzberg GW (1995) Microglia: Intrinsic immuneffector cell of the brain, Brain Res Brain Res Rev 20, 269–287.
[245] Dissing-Olesen L , Ladeby R , Nielsen HH , Toft-Hansen H , Dalmau I , Finsen B (2007) Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse, Neurosci 149, 112–122.
[246] Crews FT , Vetreno RP (2014) Neuroimmune basis of alcoholic brain damage, Int Rev Neurobiol 118, 315–357.
[247] Zou J , Crews F (2010) Induction of innate immune gene expression cascades in brain slice cultures by ethanol: Key role of NF-κB and proinflammatory cytokines, Alcohol Clin Exp Res 34, 777–789.
[248] Alfonso-Loeches S , Pascual-Lucas M , Blanco AM , Sanchez-Vera I , Guerri C (2010) Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage, J Neurosci 30, 8285–8295.
[249] Fernandez-Lizarbe S , Montesinos J , Guerri C (2013) Ethanol induces TLR4/TLR2 association, triggering an inflammatory response in microglial cells, J Neurochem 126, 261–273.
[250] Chait A , Kim F (2010) Saturated fatty acids and inflammation: Who pays the toll? Arterioscler Thromb Vasc Biol 30, 692–693.
[251] Wang Z , Liu D , Wang F , Liu S , Zhao S , Ling EA , Hao A (2012) Saturated fatty acids activate microglia via Toll-like receptor 4/NF-κB signalling, Br J Nutr 107, 229–241.
[252] Shi H , Kokoeva MV , Inouye K , Tzameli I , Yin H , Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance, J Clin Invest 116, 3015–3025.
[253] Wellen KE , Hotamisligil GS (2005) Inflammation, stress, and diabetes, J Clin Invest 115, 1111–1119.
[254] Donath MY , Shoelson SE (2011) Type 2 diabetes as an inflammatory disease, Nat Rev Immunol 11, 98–107.
[255] Kreutzberg GW (1996) Microglia: A sensor for pathological events in the CNS, Trends Neurosci 19, 312–318.
[256] Rock RB , Gekker G , Hu S , Sheng WS , Cheeran M , Lokensgard JR , Peterson PK (2004) Role of microglia in central nervous system infections, Clin Microbiol Rev 17, 942–964.
[257] Rangaraju S , Gearing M , Jin LW , Levey A (2015) Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer’s disease, J Alzheimers Dis 44, 797–808.
[258] Lenz KM , Nelson LH (2018) Microglia and beyond: Innate immune cells as regulators of brain development and behavioral function, Front Immunol 9, 698.
[259] Hwang D (2001) Modulation of the expression of cyclooxygenase-2 by fatty acids mediated through toll-like receptor 4-derived signaling pathways, FASEB J 15, 2556–2564.
[260] Belfort R , Mandarino L , Kashyap S , Wirfel K , Pratipanawatr T , Berria R , DeFronzo RA , Cusi K (2005) Dose-response effect of elevated plasma free fatty acid on insulin signaling, Diabetes 54, 1640–1648.
[261] Huber AH , Kleinfeld AM (2017) Unbound free fatty acid profiles in human plasma and the unexpected absence of unbound palmitoleate, J Lipid Res 58, 578–585.
[262] Nagy LE (2003) Recent insights into the role of the innate immune system in the development of alcoholic liver disease, Exp Biol Med (Maywood) 228, 882–890.
[263] Walter S , Letiembre M , Liu Y , Heine H , Penke B , Hao W , Bode B , Manietta N , Walter J , Schulz-Schuffer W , Fassbender K (2007) Role of the toll-like receptor 4 in neuroinflammation in Alzheimer’s disease, Cell Physiol Biochem 20, 947–956.
[264] Barak B , Feldman N , Okun E (2014) Toll-like receptors as developmental tools that regulate neurogenesis during development: An update, Front Neurosci 8, 272.
[265] Crews FT , Walter TJ , Coleman LG , Vetreno RP (2017) Toll-like receptor signaling and stages of addiction, Psychopharmacology (Berl) 234, 1483–1498.
[266] Ming GL , Song H (2011) Adult neurogenesis in the mammalian brain: Significant answers and significant questions. Neuron 70, 687–702.
[267] White AM , Signer ML , Kraus CL , Swartzwelder HS (2004) Experiential aspects of alcohol-induced blackouts among college students, Am J Drug Alcohol Abuse 30, 205–224.
[268] Sanday L , Patti CL , Zanin KA , Fernandes-Santos L , Oliveira LC , Kameda SR , Tufik S , Frussa-Filho R (2013) Ethanol-induced memory impairment in a discriminative avoidance task is state-dependent, Alcohol Clin Exp Res 37(Suppl 1), E30–E39.
[269] Ditraglia GM , Press DS , Butters N , Jernigan TL , Cermak LS , Velin RA , Shear PK , Irwin M , Schuckit M (1991) Assessment of olfactory deficits in detoxified alcoholics, Alcohol 8, 109–115.
[270] Collins MA , Corso TD , Neafsey EJ (1996) Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic “binge” intoxication with ethanol: Possible explanation for olfactory deficits in alcoholics, Alcohol Clin Exp Res 20, 284–292.
[271] Mesholam RI , Moberg PJ , Mahr RN , Doty RL (1998) Olfaction in neurodegenerative disease: A meta-analysis of olfactory functioning in Alzheimer’s and Parkinson’s diseases, Arch Neurol 55, 84–90.
[272] Murphy C , Gilmore MM , Seery CS , Salmon DP , Lasker BR (1990) Olfactory thresholds are associated with degree of dementia in Alzheimer’s disease, Neurobiol Aging 11, 465–469.
[273] Hodges J (1998) The amnestic prodrome of Alzheimer’s disease, Brain 121, 1601–1602.
[274] Weintraub S , Wicklund AH , Salmon DP (2012) The neuropsychological profile of Alzheimer disease, Cold Spring Harb Perspect Med 2, a006171.
[275] Rissman RA , Mobley WC (2011) Implication for treatment: GABAA receptors in aging, Down syndrome and Alzheimer’s disease, J Neurochem 117, 613–622.
[276] Wu Z , Guo Z , Gearing M , Chen G (2014) Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model, Nat Commun 5, 4159.
[277] Jo S , Yarishkin O , Hwang YJ , Chun YE , Park M , Woo DH , Bae JY , Kim T , Lee J , Chun H , Park HJ , Lee DY , Hong J , Kim HY , Oh SJ , Park SJ , Lee H , Yoon BE , Kim Y , Jeong Y , Shim I , Bae YC , Cho J , Kowall NW , Ryu H , Hwang E , Kim D , Lee CJ (2014) GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease, Nat Med 20, 886–896.
[278] Dahl DR , Dahl N , Samson FE Jr (1956) A study on the narcotic action of the short chain fatty acids, J Clin Invest 35, 1291–1298.
[279] White RP , Samson FE (1956) Effects of fatty acid anions on the electroencephalogram of unanesthetized rabbits, Am J Physiol 186, 271–274.
[280] Matsuzaki M , Takagi H (1967) Sleep induced by sodium butyrate in the cat, Brain Res 4, 206–222.
[281] McCandless DW (1985) Octanoic acid-induced coma and reticular formation energy metabolism, Brain Res 335, 131–137.
[282] Dahl DR (1968) Short chain fatty acid inhibition of rat brain Na-K adenosine triphosphatase, J Neurochem 15, 815–820.
[283] Perlman BJ , Goldstein DB (1984) Membrane-disordering potency and anticonvulsant action of valproic acid and other short-chain fatty acids, Mol Pharmacol 26, 83–89.
[284] Alifimoff JK , Firestone LL , Miller KW (1989) Anaesthetic potencies of primary alkanols: Implications for the molecular dimensions of the anaesthetic site, Br J Pharmacol 96, 9–16.
[285] Hau KM , Connell DW , Richardson BJ (2002) A study of the biological partitioning behavior of n-Alkanes and n-Alkanols in causing anesthetic effects, Regul Toxicol Pharmacol 35, 273–279.
[286] Deneer JW , Seinen W , Hermens JLM (1988) The acute toxicity of aldehydes to the guppy, Aquatic Toxicol 12, 185–192.
[287] Evers AS , Crowder CM (2009) Mechanisms of anesthesia and consciousness. In Clinical Anesthesia, Lippincott Williams & Wilkins, pp. 95–114.
[288] Ueda I , Suzuki A (1998) Is there a specific receptor for anesthetics? Contrary effects of alcohols and fatty acids on phase transition and bioluminescence of firefly luciferase, Biophys J 75, 1052–1057.
[289] Matsuki H , Suzuki A , Kamaya H , Ueda I (1999) Specific and non-specific binding of long-chain fatty acids to firefly luciferase: Cutoff at octanoate, Biochim Biophys Acta 1426, 143–150.
[290] Frangopol PT , Mihailescu D (2001) Interactions of some local anesthetics and alcohols with membranes, Colloids Surf B Biointerfaces 22, 3–22.
[291] Kappas A , Palmer RH (1963) Selected aspects of steroid pharmacology, Pharmacol Rev 15, 123–167.
[292] Belelli D , Lambert JJ (2005) Neurosteroids: Endogenous regulators of the GABAA receptor, Nat Rev Neurosci 6, 565–575.
[293] Orser BA (2007) Lifting the fog around anesthesia, Sci Am 296, 54–61.
[294] Bonin RP , Orser BA (2008) GABAA receptor subtypes underlying general anesthesia, Pharmacol Biochem Behav 90, 105–112.
[295] Brickley SG , Mody I (2012) Extrasynaptic GABAA receptors: Their function in the CNS and implications for disease, Neuron 73, 23–34.
[296] Cheng VY , Martin LJ , Elliott EM , Kim JH , Mount HT , Taverna FA , Roder JC , MacDonald JF , Bhambri A , Collinson N , Wafford KA , Orser BA (2006) α5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate, J Neurosci 26, 3713–3720.
[297] Nutt DJ , Besson M , Wilson SJ , Dawson GR , Lingford-Hughes AR (2007) Blockade of alcohol’s amnestic activity in humans by an [alpha]5 subtype benzodiazepine receptor inverse agonist, Neuropharmacology 53, 810–820.
[298] Sikka PK , Beaman ST , Street JA (2015) Basic Clinical Anesthesia, Springer.
[299] Farrant M , Nusser Z (2005) Variations on an inhibitory theme: Phasic and tonic activation of GABA(A) receptors, Nat Rev Neurosci 6, 215–229.
[300] Collinson N , Kuenzi FM , Jarolimek W , Maubach KA , Cothliff R , Sur C , Smith A , Otu FM , Howell O , Atack JR , McKernan RM , Seabrook GR , Dawson GR , Whiting PJ , Rosahl TW (2002) Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor, J Neurosci 22, 5572–5580.
[301] Shen H , Sabaliauskas N , Sherpa A , Fenton AA , Stelzer A , Aoki C , Smith SS (2010) A critical role for alpha4betadelta GABAA receptors in shaping learning deficits at puberty in mice, Science 327, 1515–1518.
[302] Clarkson AN , Huang BS , Macisaac SE , Mody I , Carmichael ST (2010) Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke, Nature 468, 305–309.
[303] Liu Y , Namba T , Liu J , Suzuki R , Shioda S , Seki T (2010) Glial fibrillary acidic protein-expressing neural progenitors give rise to immature neurons via early intermediate progenitors expressing both glial fibrillary acidic protein and neuronal markers in the adult hippocampus, Neuroscience 166, 241–251.
[304] Martin LJ , Zurek AA , MacDonald JF , Roder JC , Jackson MF , Orser BA (2010) α5GABAA receptor activity sets the threshold for long-term potentiation and constrains hippocampus-dependent memory, J Neurosci 30, 5269–5282.
[305] Whissell PD , Eng D , Lecker I , Martin LJ , Wang DS , Orser BA (2013) Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus, Front Neural Circuits 7, 146.
[306] Grover LM , Lambert NA , Schwartzkroin PA , Teyler TJ (1993) Role of HCO3- ions in depolarizing GABAA receptor-mediated responses in pyramidal cells of rat hippocampus, J Neurophysiol 69, 1541–1555.
[307] Li K , Xu E (2008) The role and the mechanism of γ-aminobutyric acid during central nervous system development, Neurosci Bull 24, 195–200.
[308] Sigel E , Steinmann ME (2012) Structure, function, and modulation of GABAA receptors, J Biol Chem 287, 40224–40231.
[309] Kaila K (1994) Ionic basis of GABAA receptor channel function in the nervous system, Prog Neurobiol 42, 489–537.
[310] Petrini EM , Marchionni I , Zacchi P , Sieghart W , Cherubini E (2004) Clustering of extrasynaptic GABAA receptors modulates tonic inhibition in cultured hippocampal neurons, J Biol Chem 279, 45833–45843.
[311] Jia F , Pignataro L , Schofield CM , Yue M , Harrison NL , Goldstein PA (2005) An extrasynaptic GABAA receptor mediates tonic inhibition in thalamic VB neurons, J Neurophysiol 94, 4491–4501.
[312] Orser BA , McAdam LC , Roder S , MacDonald JF (1998) General anaesthetics and their effects on GABAA receptor desensitization, Toxicol Lett 100-101, 217–224.
[313] Krasowski MD (2003) Contradicting a unitary theory of general anesthetic action: A history of three compounds from 1901 to 2001, Bull Anesth Hist 21, 1, 4-8, 21 passim.
[314] Krasowski MD , Harrison NL (1999) General anaesthetic actions on ligand-gated ion channels, Cell Mol Life Sci 55, 1278–1303.
[315] MacIver MB (2014) Anesthetic agent-specific effects on synaptic inhibition, Anesth Analg 119, 558–569.
[316] Yeung JYT , Canning KJ , Zhu G , Pennefather P , MacDonald JF , Orser BA (2003) Tonically activated GABAA receptors in hippocampal neurons are high-affinity, low-conductance sensors for extracellular GABA, Mol Pharmacol 63, 2–8.
[317] Liu X , Wang Q , Haydar TF , Bordey A (2005) Nonsynaptic GABA signaling in postnatal subventricular zone controls GFAP-expressing progenitor proliferation, Nat Neurosci 8, 1179–1187.
[318] Bordey A (2007) Enigmatic GABAergic networks in adult neurogenic zones, Brain Res Rev 53, 124–134.
[319] Paik NJ , Yang E (2014) Role of GABA plasticity in stroke recovery, Neural Regen Res 9, 2026–2028.
[320] Clarkson AN (2012) Perisynaptic GABA receptors the overzealous protector, Adv Pharmacol Sci 2012, 708428.
[321] Wei W , Faria LC , Mody I (2004) Low ethanol concentrations selectively augment the tonic inhibition mediated by Δ subunit-containing GABAA receptors in hippocampal neurons, J Neurosci 24, 8379–8382.
[322] Meera P , Olsen RW , Otis TS , Wallner M (2010) Alcohol- and alcohol antagonist-sensitive human GABAA receptors: Tracking δ subunit incorporation into functional receptors, Mol Pharmacol 78, 918–924.
[323] Mandyam CD (2013) Neurogenesis and addictive disorders. In Biological Research on Addiction: Comprehensive Addictive Behaviors and Disorders, Academic Press, pp. 760.
[324] Eriksson PS , Perfilieva E , Björk-Eriksson T , Alborn AM , Nordborg C , Peterson DA , Gage FH (1998) Neurogenesis in the adult human hippocampus, Nat Med 4, 1313–1317.
[325] Lim DA , Alvarez-Buylla A (2016) The adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) neurogenesis, Cold Spring Harb Perspect Biol 8, a018820.
[326] Walker CO , McCandless DW , McGarry JD , Schenker S (1970) Cerebral energy metabolism in short-chain fatty acid-induced coma, J Lab Clin Med 76, 569–583.
[327] Pringle MJ , Brown KB , Miller KW (1981) Can the lipid theories of anesthesia account for the cutoff in anesthetic potency in homologous series of alcohols? Mol Pharmacol 19, 49–55.
[328] Wong SM , Fong E , Tauck DL , Kendig JJ (1997) Ethanol as a general anesthetic: Actions in spinal cord, Eur J Pharmacol 329, 121–127.
[329] Chiou JS , Ma SM , Kamaya H , Ueda I (1990) Anesthesia cutoff phenomenon: Interfacial hydrogen bonding, Science 248, 583–585.
[330] Wick MJ , Mihic SJ , Ueno S , Mascia MP , Trudell JR , Brozowski SJ , Ye Q , Harrison NL , Harris RA (1998) Mutations of γ-aminobutyric acid and glycine receptors change alcohol cutoff: Evidence for an alcohol receptor? Proc Natl Acad Sci U S A 95, 6504–6509.
[331] Lugli AK , Yost CS , Kindler CH (2009) Anaesthetic mechanisms: Update on the challenge of unravelling the mystery of anaesthesia, Eur J Anaesthesiol 26, 807–820.
[332] Davies M (2003) The role of GABAA receptors in mediating the effects of alcohol in the central nervous system, J Psychiatry Neurosci 28, 263–274.
[333] Lees G , Edwards MD , Hassoni AA , Ganellin CR , Galanakis D (1998) Modulation of GABA(A) receptors and inhibitory synaptic currents by the endogenous CNS sleep regulator cis-9,10-octadecenoamide (cOA), Br J Pharmacol 124, 873–882.
[334] Laws D , Verdon B , Coyne L , Lees G (2001) Fatty acid amides are putative endogenous ligands for anaesthetic recognition sites in mammalian CNS, Br J Anaesth 87, 380–384.
[335] Coyne L , Lees G , Nicholson RA , Zheng J , Neufield KD (2002) The sleep hormone oleamide modulates inhibitory ionotropic receptors in mammalian CNS in vitro, Br J Pharmacol 135, 1977–1987.
[336] Hanada R , Tatara T , Iwao Y (2004) Antagonizing potencies of saturated and unsaturated long-chain free fatty acids to isoflurane in goldfish, J Anesth 18, 89–93.
[337] Yamakura T (2004) Volatile anesthetic antagonism by long-chain free fatty acids, J Anesth 18, 71–72.
[338] Koenig JA , Martin IL (1992) Effect of free fatty acids on GABAA receptor ligand binding, Biochem Pharmacol 44, 11–15.
[339] Witt M , Nielsen M (1994) Characterization of the influence of unsaturated free fatty acids on brain GABA/benzodiazepine receptor binding in vitro, J Neurochem 62, 1432–1439.
[340] Zhang L , Xiong W (2009) Modulation of the Cys-loop ligand-gated ion channels by fatty acid and cannabinoids. In Vitamins & Hormones, Academic Press, pp. 315–335.
[341] Laterra J , Keep R , Betz LA , Goldstein GW (1999) Blood-brain barrier. Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 6th edition, SiegelGJ, AgranoffBW, AlbersRW, FisherSK, UhlerMD, eds. Lippincott-Raven, Philadelphia.
[342] Bodovitz S , Klein WL (1996) Cholesterol modulates -secretase cleavage of amyloid precursor protein, J Biol Chem 271, 4436–4440.
[343] Kojro E , Gimpl G , Lammich S , Marz W , Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10, Proc Natl Acad Sci U S A 98, 5815–5820.
[344] Simons M , Keller P , De Strooper B , Beyreuther K , Dotti CG , Simons K (1998) Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons, Proc Natl Acad Sci U S A 95, 6460–6464.
[345] Ehehalt R , Keller P , Haass C , Thiele C , Simons K (2003) Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts, J Cell Biol 160, 113–123.
[346] Nixon RA (2017) Amyloid precursor protein and endosomal–lysosomal dysfunction in Alzheimer’s disease: Inseparable partners in a multifactorial disease, FASEB J 31, 2729–2743.
[347] Habchi J , Chia S , Galvagnion C , Michaels TCT , Bellaiche MMJ , Ruggeri FS , Sanguanini M , Idini I , Kumita JR , Sparr E , Linse S , Dobson CM , Knowles TPJ , Vendruscolo M (2018) Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes, Nat Chem 10, 673–683.
[348] Rushworth JV , Hooper NM (2010) Lipid rafts: Linking Alzheimer’s amyloid-β production, aggregatio