This article examines the relationship between cholesterol levels and Alzheimer’s disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention.
RefoloLM, MalesterB, LaFrancoisJ, Bryant-ThomasT, WangR, TintGS, SambamurtiK, DuffK, PappollaMA (2000) Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis7, 321–331.
3.
RefoloLM, PappollaMA, LaFrancoisJ, MalesterB, SchmidtSD, Thomas-BryantT, TintGS, WangR, MerckenM, PetanceskaSS, DuffKE (2001) A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer’s disease. Neurobiol Dis8, 890–899.
4.
PappollaMA, Bryant-ThomasTK, HerbertD, PachecoJ, Fabra GarciaM, ManjonM, GironesX, HenryTL, MatsubaraE, ZambonD, WolozinB, SanoM, Cruz-SanchezFF, ThalLJ, PetanceskaSS, RefoloLM (2003) Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology61, 199–205.
5.
NotkolaIL, SulkavaR, PekkanenJ, ErkinjunttiT, EhnholmC, KivinenP, TuomilehtoJ, NissinenA (1998) Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer’s disease. Neuroepidemiology17, 14–20.
6.
KivipeltoM, SolomonA (2006) Cholesterol as a risk factor for Alzheimer’s disease – epidemiological evidence. Acta Neurol Scand Suppl185, 50–57.
7.
SolomonA, KivipeltoM, WolozinB, ZhouJ, WhitmerRA (2009) Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later. Dement Geriatr Cogn Disord28, 75–80.
8.
PowerMC, RawlingsA, SharrettAR, Bandeen-RocheK, CoreshJ, BallantyneCM, PokharelY, MichosED, PenmanA, AlonsoA, KnopmanD, MosleyTH, GottesmanRF (2018) Association of midlife lipids with 20-year cognitive change: A cohort study. Alzheimers Dement14, 167–177.
9.
ReitzC, TangMX, LuchsingerJ, MayeuxR (2004) Relation of plasma lipids to Alzheimer disease and vascular dementia. Arch Neurol61, 705–714.
10.
ReitzC, LuchsingerJ, TangMX, ManlyJ, MayeuxR (2005) Impact of plasma lipids and time on memory performance in healthy elderly without dementia. Neurology64, 1378–1383.
11.
ReitzC, TangMX, ManlyJ, SchupfN, MayeuxR, LuchsingerJA (2008) Plasma lipid levels in the elderly are not associated with the risk of mild cognitive impairment. Dement Geriatr Cogn Disord25, 232–237.
12.
MielkeMM, ZandiPP, SjögrenM, GustafsonD, OstlingS, SteenB, SkoogI (2005) High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology64, 1689–1695.
13.
Sánchez-FerroA, Benito-LeónJ, MitchellAJ, Bermejo-ParejaF (2013) A review of the potential therapeutic role of statins in the treatment of Alzheimer’s disease: Current research and opinion. Neuropsychiatr Dis Treat9, 55–63.
14.
ShepardsonNE, ShankarGM, SelkoeDJ (2011) Cholesterol level and statin use in Alzheimer disease: I. Review of epidemiological and preclinical studies. Arch Neurol68, 1239–1244.
15.
SantanelloNC, BarberBL, ApplegateWB, ElamJ, CurtisC, HunninghakeDB, GordonDJ (1997) Effect of pharmacologic lipid lowering on health-related quality of life in older persons: Results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot Study. J Am Geriatr Soc45, 8–14.
16.
KalmijnS, FoleyD, WhiteL, BurchfielCM, CurbJD, PetrovitchH, RossGW, HavlikRJ, LaunerLJ (2000) Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol20, 2255–2260.
17.
VemuriP, LesnickTG, PrzybelskiSA, KnopmanDS, LoweVJ, Graff-RadfordJ, RobertsRO, MielkeMM, MachuldaMM, PetersenRC, JackCR, Jr. (2017) Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann Neurol82, 706–718.
18.
LaunerLJ, WhiteLR, PetrovitchH, RossGW, CurbJD (2001) Cholesterol and neuropathologic markers of AD: A population-based autopsy study. Neurology57, 1447–1452.
19.
MartínMG, PfriegerF, DottiCG (2014) Cholesterol in brain disease: Sometimes determinant and frequently implicated. EMBO Rep15, 1036–1052.
20.
PappollaMA, SmithMA, Bryant-ThomasT, BazanN, PetanceskaS, PerryG, ThalLJ, SanoM, RefoloLM (2002) Cholesterol, oxidative stress, and Alzheimer’s disease: Expanding the horizons of pathogenesis. Free Radic Biol Med33, 173–181.
21.
AbildayevaK, JansenPJ, Hirsch-ReinshagenV, BloksVW, BakkerAH, RamaekersFC, de VenteJ, GroenAK, WellingtonCL, KuipersF, MulderM (2006) 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem281, 12799–12808.
22.
HayashiH (2011) Lipid metabolism and glial lipoproteins in the central nervous system. Biol Pharm Bull34, 453–461.
23.
WangY, HaoL, WangT, LiuW, WangL, JuM, FengW, XiaoR (2022) 27-hydroxycholesterol-induced dysregulation of cholesterol metabolism impairs learning and memory ability in ApoE epsilon4 transgenic mice. Int J Mol Sci23, 11639.
24.
GambaP, GiannelliS, StaurenghiE, TestaG, SotteroB, BiasiF, PoliG, LeonarduzziG (2021) The controversial role of 24-S-hydroxycholesterol in Alzheimer’s disease. Antioxidants (Basel)10, 740.
25.
WangY, MunetonS, SjövallJ, JovanovicJN, GriffithsWJ (2008) The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons: Quantitative changes to the cortical neuron proteome. J Proteome Res7, 1606–1614.
26.
JanowskiBA, WillyPJ, DeviTR, FalckJR, MangelsdorfDJ (1996) An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature383, 728–731.
27.
WangY, KumarN, CrumbleyC, GriffinPR, BurrisTP (2010) A second class of nuclear receptors for oxysterols: Regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol). Biochim Biophys Acta1801, 917–923.
28.
StevenMP, JamesJD, AlbertJR, GabrielMB, BrianYC, RebeccaSH, DevonCC, AndrewJL, Hong-JinS, YukitoshiI, StevenJM, CharlesFZ (2013) The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of-methyl-D-aspartate receptors. J Neurosci33, 17290.
29.
GambaP, LeonarduzziG, TamagnoE, GuglielmottoM, TestaG, SotteroB, GargiuloS, BiasiF, MauroA, VinaJ, PoliG (2011) Interaction between 24-hydroxycholesterol, oxidative stress, and amyloid-beta in amplifying neuronal damage in Alzheimer’s disease: Three partners in crime. Aging Cell10, 403–417.
30.
DiasIHK, ShokrH, ShephardF, ChakrabartiL (2022) Oxysterols and oxysterol sulfates in Alzheimer’s disease brain and cerebrospinal fluid. J Alzheimers Dis87, 1527–1536.
31.
WongMY, LewisM, DohertyJJ, ShiY, CashikarAG, AmelianchikA, TymchukS, SullivanPM, QianM, CoveyDF, PetskoGA, HoltzmanDM, PaulSM, LuoW (2020) 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner. J Neuroinflammation17, 192.
32.
GcJB, ChenJ, PokharelSM, MohantyI, MariasoosaiC, ObiP, PanipintoP, BandyopadhyayS, BoseS, NatesanS (2023) Molecular basis for the recognition of 24-(S)-hydroxycholesterol by integrin αvβ3. Sci Rep13, 9166.
33.
Sandebring-MattonA, GoikoleaJ, BjörkhemI, PaternainL, KemppainenN, LaatikainenT, NganduT, RinneJ, SoininenH, Cedazo-MinguezA, SolomonA, KivipeltoM (2021) 27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial. Alzheimers Res Ther13, 56.
34.
HuebbeP, RimbachG (2017) Evolution of human apolipoprotein E (APOE) isoforms: Gene structure, protein function and interaction with dietary factors. Ageing Res Rev37, 146–161.
35.
ChenJ, LiQ, WangJ (2011) Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc Natl Acad Sci U S A108, 14813–14818.
36.
StrittmatterWJ, SaundersAM, SchmechelD, Pericak-VanceM, EnghildJ, SalvesenGS, RosesAD (1993) Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A90, 1977–1981.
37.
WaltersS, ContrerasAG, EissmanJM, MukherjeeS, LeeML, ChoiSE, ScollardP, TrittschuhEH, MezJB, BushWS, KunkleBW, NajAC, PetersonA, GiffordKA, CuccaroML, CruchagaC, Pericak-VanceMA, FarrerLA, WangLS, HainesJL, JeffersonAL, KukullWA, KeeneCD, SaykinAJ, ThompsonPM, MartinER, BennettDA, BarnesLL, SchneiderJA, CranePK, HohmanTJ, DumitrescuL (2023) Associations of sex, race, and apolipoprotein E alleles with multiple domains of cognition among older adults. JAMA Neurol80, 929–939.
38.
FarrerLA, CupplesLA, HainesJL, HymanB, KukullWA, MayeuxR, MyersRH, Pericak-VanceMA, RischN, van DuijnCM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA278, 1349–1356.
39.
VélezJI, LoperaF, Sepulveda-FallaD, PatelHR, JoharAS, ChuahA, TobónC, RiveraD, VillegasA, CaiY, PengK, ArkellR, CastellanosFX, AndrewsSJ, Silva LaraMF, CreaghPK, EastealS, de LeonJ, WongML, LicinioJ, MastronardiCA, Arcos-BurgosM (2016) APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease. Mol Psychiatry21, 916–924.
40.
YamazakiY, ZhaoN, CaulfieldTR, LiuCC, BuG (2019) Apolipoprotein E and Alzheimer disease: Pathobiology and targeting strategies. Nat Rev Neurol15, 501–518.
41.
MachuldaMM, JonesDT, VemuriP, McDadeE, AvulaR, PrzybelskiS, BoeveBF, KnopmanDS, PetersenRC, JackCRJr. (2011) Effect of APOE ɛ4 status on intrinsic network connectivity in cognitively normal elderly subjects. Arch Neurol68, 1131–1136.
42.
LiuCC, LiuCC, KanekiyoT, XuH, BuG (2013) Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat Rev Neurol9, 106–118.
43.
WilliamsT, BorcheltDR, ChakrabartyP (2020) Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease. Mol Neurodegener15, 8.
CamusMC, ChapmanMJ, ForgezP, LaplaudPM (1983) Distribution and characterization of the serum lipoproteins and apoproteins in the mouse, Mus musculus. J Lipid Res24, 1210–1228.
46.
DavidsonMH (2010) Update on CETP inhibition. J Clin Lipidol4, 394–398.
47.
SullivanPM, MezdourH, QuarfordtSH, MaedaN (1998) Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2. J Clin Invest102, 130–135.
48.
MethiaN, AndréP, Hafezi-MoghadamA, EconomopoulosM, ThomasKL, WagnerDD (2001) ApoE deficiency compromises the blood brain barrier especially after injury. Mol Med7, 810–815.
49.
GrootendorstJ, BourA, VogelE, KelcheC, SullivanPM, DodartJC, BalesK, MathisC (2005) Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior. Behav Brain Res159, 1–14.
50.
PetanceskaSS, DeRosaS, SharmaA, DiazN, DuffK, TintSG, RefoloLM, PappollaM (2003) Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci20, 395–406.
51.
KojroE, GimplG, LammichS, MarzW, FahrenholzF (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. Proc Natl Acad Sci U S A98, 5815–5820.
52.
SimonsM, KellerP, De StrooperB, BeyreutherK, DottiCG, SimonsK (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci U S A95, 6460–6464.
53.
YipCM, EltonEA, DarabieAA, MorrisonMR, McLaurinJ (2001) Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis and neurotoxicity. J Mol Biol311, 723–734.
54.
MizunoT, NakataM, NaikiH, MichikawaM, WangR, HaassC, YanagisawaK (1999) Cholesterol-dependent generation of a seeding amyloid beta-protein in cell culture. J Biol Chem274, 15110–15114.
55.
WangT, JiaH (2023) The sigma receptors in Alzheimer’s disease: New potential targets for diagnosis and therapy. Int J Mol Sci24, 12025.
56.
Lane-DonovanC, PhilipsGT, HerzJ (2014) More than cholesterol transporters: Lipoprotein receptors in CNS function and neurodegeneration. Neuron83, 771–787.
57.
MarzoloMP, BuG (2009) Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer’s disease. Semin Cell Dev Biol20, 191–200.
58.
ZambónD, QuintanaM, MataP, AlonsoR, BenaventJ, Cruz-SánchezF, GichJ, PocovíM, CiveiraF, CapurroS, BachmanD, SambamurtiK, NicholasJ, PappollaMA (2010) Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Am J Med123, 267–274.
59.
AlenghatFJ, DavisAM (2019) Management of blood cholesterol. JAMA321, 800–801.
60.
LewingtonS, WhitlockG, ClarkeR, SherlikerP, EmbersonJ, HalseyJ, QizilbashN, PetoR, CollinsR (2007) Blood cholesterol and vascular mortality by age, sex, and blood pressure: A meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet370, 1829–1839.
61.
EndoA (1992) The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res33, 1569–1582.
62.
McKenneyJM, GanzP, WigginsBS, SaseenJS (2009) CHAPTER 22 – Statins. In Clinical Lipidology, BallantyneCM, ed. W.B. Saunders, Philadelphia, pp. 253–280.
63.
JacobsenW, KirchnerG, HallenslebenK, MancinelliL, DetersM, HackbarthI, BenetLZ, SewingKF, ChristiansU (1999) Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos27, 173–179.
64.
RudajevV, NovotnyJ (2023) Cholesterol-dependent amyloid β production: Space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol. Cell Biosci13, 171.
65.
LiaoJK, LaufsU (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol45, 89–118.
66.
PordelS, McCloskeyAP, AlmahmeedW, SahebkarA (2024) The protective effects of statins in traumatic brain injury. Pharmacol Rep76, 235–250.
67.
WolozinB, KellmanW, RuosseauP, CelesiaGG, SiegelG (2000) Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol57, 1439–1443.
68.
YaffeK, Barrett-ConnorE, LinF, GradyD (2002) Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol59, 378–384.
69.
ZandiPP, SparksDL, KhachaturianAS, TschanzJ, NortonM, SteinbergM, Welsh-BohmerKA, BreitnerJC (2005) Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry62, 217–224.
70.
ReaTD, BreitnerJC, PsatyBM, FitzpatrickAL, LopezOL, NewmanAB, HazzardWR, ZandiPP, BurkeGL, LyketsosCG, BernickC, KullerLH (2005) Statin use and the risk of incident dementia: The Cardiovascular Health Study. Arch Neurol62, 1047–1051.
71.
JickH, ZornbergGL, JickSS, SeshadriS, DrachmanDA (2000) Statins and the risk of dementia. Lancet356, 1627–1631.
72.
LiG, LarsonEB, SonnenJA, ShoferJB, PetrieEC, SchantzA, PeskindER, RaskindMA, BreitnerJC, MontineTJ (2007) Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology69, 878–885.
73.
MasseI, BordetR, DeplanqueD, KhedrAA, RichardF, LibersaC, PasquierF (2005) Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease. J Neurol Neurosurg Psychiatry76, 1624–1629.
74.
CramerC, HaanMN, GaleaS, LangaKM, KalbfleischJD (2008) Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology71, 344–350.
75.
HaagMD, HofmanA, KoudstaalPJ, StrickerBH, BretelerMM (2009) Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J Neurol Neurosurg Psychiatry80, 13–17.
76.
WolozinB, WangSW, LiNC, LeeA, LeeTA, KazisLE (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med5, 20.
77.
KempEC, EbnerMK, RamananS, GodekTA, PughEA, BartlettHH, McDonaldJW, MeccaMC, van DyckCH, MeccaAP (2020) Statin use and risk of cognitive decline in the ADNI cohort. Am J Geriatr Psychiatry28, 507–517.
78.
PetekB, HäbelH, XuH, Villa-LopezM, KalarI, HoangMT, MaioliS, PereiraJB, MostafaeiS, WinbladB, Gregoric KrambergerM, EriksdotterM, Garcia-PtacekS (2023) Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: A longitudinal registry-based cohort study. Alzheimers Res Ther15, 220.
79.
ArvanitakisZ, SchneiderJA, WilsonRS, BieniasJL, KellyJF, EvansDA, BennettDA (2008) Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology70, 1795–1802.
80.
AdhikariA, TripathyS, ChuziS, PetersonJ, StoneNJ (2021) Association between statin use and cognitive function: A systematic review of randomized clinical trials and observational studies. J Clin Lipidol15, 22–32.e12.
81.
OlmastroniE, MolariG, De BeniN, ColpaniO, GalimbertiF, GazzottiM, ZambonA, CatapanoAL, CasulaM (2022) Statin use and risk of dementia or Alzheimer’s disease: A systematic review and meta-analysis of observational studies. Eur J Prev Cardiol29, 804–814.
82.
GeifmanN, BrintonRD, KennedyRE, SchneiderLS, ButteAJ (2017) Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease. Alzheimers Res Ther9, 10.
83.
PolyTN, IslamMM, WaltherBA, YangHC, WuCC, LinMC, LiYC (2020) Association between use of statin and risk of dementia: A meta-analysis of observational studies. Neuroepidemiology54, 214–226.
84.
(2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet360, 7–22.
85.
JonesRW, KivipeltoM, FeldmanH, SparksL, DoodyR, WatersDD, Hey-HadaviJ, BreaznaA, SchindlerRJ, RamosH (2008) The Atorvastatin/Donepezil in Alzheimer’s Disease Study (LEADe): Design and baseline characteristics. Alzheimers Dement4, 145–153.
86.
ShepherdJ, BlauwGJ, MurphyMB, BollenEL, BuckleyBM, CobbeSM, FordI, GawA, HylandM, JukemaJW, KamperAM, MacfarlanePW, MeindersAE, NorrieJ, PackardCJ, PerryIJ, StottDJ, SweeneyBJ, TwomeyC, WestendorpRG (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): A randomised controlled trial. Lancet360, 1623–1630.
87.
SanoM, BellKL, GalaskoD, GalvinJE, ThomasRG, van DyckCH, AisenPS (2011) A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology77, 556–563.
88.
McGuinnessB, O’HareJ, CraigD, BullockR, MaloufR, PassmoreP (2010) Statins for the treatment of dementia. Cochrane Database Syst Rev, CD007514.
89.
CarlssonCM, GleasonCE, HessTM, MorelandKA, BlazelHM, KoscikRL, SchreiberNT, JohnsonSC, AtwoodCS, PuglielliL, HermannBP, McBridePE, SteinJH, SagerMA, AsthanaS (2008) Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer’s disease. J Alzheimers Dis13, 187–197.
90.
RiekseRG, LiG, PetrieEC, LeverenzJB, VavrekD, VuleticS, AlbersJJ, MontineTJ, LeeVM, LeeM, SeubertP, GalaskoD, SchellenbergGD, HazzardWR, PeskindER (2006) Effect of statins on Alzheimer’s disease biomarkers in cerebrospinal fluid. J Alzheimers Dis10, 399–406.
91.
LudewigB, JäggiM, DumreseT, Brduscha-RiemK, OdermattB, HengartnerH, ZinkernagelRM (2001) Hypercholesterolemia exacerbates virus-induced immunopathologic liver disease via suppression of antiviral cytotoxic T cell responses. J Immunol166, 3369–3376.
92.
RoselaarSE, DaughertyA (1998) Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes. J Lipid Res39, 1740–1743.
93.
de BontN, NeteaMG, DemackerPN, VerschuerenI, KullbergBJ, van DijkKW, van der MeerJW, StalenhoefAF (1999) Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. J Lipid Res40, 680–685.
94.
ColeGA, NathansonN, PrendergastRA (1972) Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature238, 335–337.
95.
de OliveiraJ, MoreiraELG, de BemAF (2024) Beyond cardiovascular risk: Implications of Familial hypercholesterolemia on cognition and brain function. Ageing Res Rev93, 102149.
96.
HongDY, LeeDH, LeeJY, LeeEC, ParkSW, LeeMR, OhJS (2022) Relationship between brain metabolic disorders and cognitive impairment: LDL receptor defect. Int J Mol Sci23, 8384.
