Associations of Alcohol Consumption with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study
Restricted accessResearch articleFirst published online August 3, 2021
Associations of Alcohol Consumption with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study
The relationship between alcohol consumption and Alzheimer’s disease (AD) pathology is unclear. Amyloid-β (Aβ) and tau biomarkers in cerebrospinal fluid (CSF) have been proven valuable in establishing prognosis in pre-clinical AD.
Objective:
We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects.
Methods:
A total of 806 cognitively intact participants who had measurements of CSF Aβ, pTau, and total Tau proteins and drinking characteristics were included from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) study. Linear and logistic regression analyses were utilized to explore the associations of alcohol consumption with CSF AD biomarkers. We examined the interaction effects of age, gender, and apolipoprotein epsilon (APOE) ɛ4 status on the relationships between the frequency of drinking and CSF biomarkers.
Results:
The multiple linear regression analyses revealed significant differences in CSF AD biomarkers between infrequent drinking (< 1 times/week) and frequent drinking groups (≥1 times/week). Participants in frequent drinking group had higher CSF p-tau/Aβ42 and tTau/Aβ42. Frequent drinking was significantly associated with greater pTau and tTau abnormalities compared to the infrequent drinking group in older (> 65 years) participants.
Conclusion:
The present study showed significant associations between drinking frequency and CSF AD biomarkers in cognitively intact older adults. Alcohol consumption may have an influence on AD by modulating amyloid deposition and tau phosphorylation in the preclinical stage.
van der KantR, GoldsteinLSB, OssenkoppeleR (2020) Amyloid-beta-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci21, 21–35.
2.
PrinsND, van SwietenJC (2010) Alzheimer disease: MRI and CSF biomarkers in AD–accuracy and temporal change. Nat Rev Neurol6, 650–651.
3.
MolinuevoJL, AytonS, BatrlaR, BednarMM, BittnerT, CummingsJ, FaganAM, HampelH, MielkeMM, MikulskisA, O’BryantS, ScheltensP, SevignyJ, ShawLM, SoaresHD, TongG, TrojanowskiJQ, ZetterbergH, BlennowK (2018) Current state of Alzheimer’s fluid biomarkers. Acta Neuropathol136, 821–853.
4.
BlennowK, HampelH, WeinerM, ZetterbergH (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol6, 131–144.
5.
RitchieC, SmailagicN, Noel-StorrAH, UkoumunneO, LaddsEC, MartinS (2017) CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev3, CD010803.
6.
HanssonO, SeibylJ, StomrudE, ZetterbergH, TrojanowskiJQ, BittnerT, LifkeV, CorradiniV, EichenlaubU, BatrlaR, BuckK, ZinkK, RabeC, BlennowK, ShawLM, Swedish Bio Fsg, Alzheimer’s Disease Neuroimaging Initiative (2018) CSF biomarkers of Alzheimer’s disease concord with amyloid-beta PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement14, 1470–1481.
7.
LangballeEM, AskH, HolmenJ, StordalE, SaltvedtI, SelbaekG, FikseaunetA, BerghS, NafstadP, TambsK (2015) Alcohol consumption and risk of dementia up to 27 years later in a large, population-based sample: The HUNT study, Norway. Eur J Epidemiol30, 1049–1056.
8.
JarvenpaaT, RinneJO, KoskenvuoM, RaihaI, KaprioJ (2005) Binge drinking in midlife and dementia risk. Epidemiology16, 766–771.
9.
SchwarzingerM, PollockBG, HasanOSM, DufouilC, RehmJ, QalyDays Study Group (2018) Contribution of alcohol use disorders to the burden of dementia in France 2008-13: A nationwide retrospective cohort study. Lancet Public Health3, e124–e132.
10.
RuitenbergA, van SwietenJC, WittemanJC, MehtaKM, van DuijnCM, HofmanA, BretelerMM (2002) Alcohol consumption and risk of dementia: The Rotterdam Study. Lancet359, 281–286.
11.
XuW, WangH, WanY, TanC, LiJ, TanL, YuJT (2017) Alcohol consumption and dementia risk: A dose-response meta-analysis of prospective studies. Eur J Epidemiol32, 31–42.
MunozG, UrrutiaJC, BurgosCF, SilvaV, AguilarF, SamaM, YehHH, OpazoC, AguayoLG (2015) Low concentrations of ethanol protect against synaptotoxicity induced by Abeta in hippocampal neurons. Neurobiol Aging36, 845–856.
14.
BateC, WilliamsA (2011) Ethanol protects cultured neurons against amyloid-beta and alpha-synuclein-induced synapse damage. Neuropharmacology61, 1406–1412.
15.
HoffmanJL, FaccidomoS, KimM, TaylorSM, AgogliaAE, MayAM, SmithEN, WongLC, HodgeCW (2019) Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer’s disease. Int Rev Neurobiol148, 169–230.
16.
KimJW, ByunMS, YiD, LeeJH, KoK, JeonSY, SohnBK, LeeJY, KimYK, ShinSA, SohnCH, LeeDY, GroupKR (2020) Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study. PLoS Med17, e1003022.
17.
KokEH, KarppinenTT, LuotoT, AlafuzoffI, KarhunenPJ (2016) Beer drinking associates with lower burden of amyloid beta aggregation in the brain: Helsinki Sudden Death Series. Alcohol Clin Exp Res40, 1473–1478.
18.
KochM, CostanzoS, FitzpatrickAL, LopezOL, DeKoskyS, KullerLH, PriceJ, MackeyRH, JensenMK, MukamalKJ (2020) Alcohol consumption, brain amyloid-beta deposition, and brain structural integrity among older adults free of dementia. J Alzheimers Dis74, 509–519.
AlbertMS, DeKoskyST, DicksonD, DuboisB, FeldmanHH, FoxNC, GamstA, HoltzmanDM, JagustWJ, PetersenRC, SnyderPJ, CarrilloMC, ThiesB, PhelpsCH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 270–279.
21.
McKhannGM, KnopmanDS, ChertkowH, HymanBT, JackCRJr, KawasCH, KlunkWE, KoroshetzWJ, ManlyJJ, MayeuxR, MohsRC, MorrisJC, RossorMN, ScheltensP, CarrilloMC, ThiesB, WeintraubS, PhelpsCH (2011) The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 263–269.
22.
ReimanEM, ChenK, LiuX, BandyD, YuM, LeeW, AyutyanontN, KepplerJ, ReederSA, LangbaumJB, AlexanderGE, KlunkWE, MathisCA, PriceJC, AizensteinHJ, DeKoskyST, CaselliRJ (2009) Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A106, 6820–6825.
23.
MaLZ, TanL, BiYL, ShenXN, XuW, MaYH, LiHQ, DongQ, YuJT (2020) Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: The CABLE study. Mol Neurodegener15, 25.
24.
MorrisJC, RoeCM, XiongC, FaganAM, GoateAM, HoltzmanDM, MintunMA (2010) APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol67, 122–131.
25.
HwangJ, JeongJH, YoonSJ, ParkKW, KimEJ, YoonB, JangJW, KimHJ, HongJY, LeeJM, ParkH, KangJH, ChoiYH, ParkG, HongJ, ByunMS, YiD, KimYK, LeeDY, ChoiSH (2019) Clinical and biomarker characteristics according to clinical spectrum of Alzheimer’s disease (AD) in the validation cohort of Korean Brain Aging Study for the early diagnosis and prediction of AD. J Clin Med8, 341.
26.
JangH, KimHJ, ParkS, ParkYH, ChoeY, ChoH, LyooCH, YoonU, LeeJS, KimY, KimSJ, KimJP, JungYH, RyuYH, ChoiJY, MoonSH, SeongJK, DeCarliC, WeinerMW, LockhartSN, ChoSH, NaDL, SeoSW (2020) Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients. Eur J Nucl Med Mol Imaging47, 292–303.
27.
HouY, DanX, BabbarM, WeiY, HasselbalchSG, CroteauDL, BohrVA (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol15, 565–581.
28.
RossorMN, FoxNC, MummeryCJ, SchottJM, WarrenJD (2010) The diagnosis of young-onset dementia. Lancet Neurol9, 793–806.
29.
KimJW, LeeDY, LeeBC, JungMH, KimH, ChoiYS, ChoiIG (2012) Alcohol and cognition in the elderly: A review. Psychiatry Investig9, 8–16.
MukamalKJ, KullerLH, FitzpatrickAL, LongstrethWTJr., MittlemanMA, SiscovickDS (2003) Prospective study of alcohol consumption and risk of dementia in older adults. JAMA289, 1405–1413.
32.
WeyererS, SchaufeleM, WieseB, MaierW, TebarthF, van den BusscheH, PentzekM, BickelH, LuppaM, Riedel-HellerSG, German AgeCoDe Study group (German Study on Ageing, Cognition and Dementia in Primary Care Patients) (2011) Current alcohol consumption and its relationship to incident dementia: Results from a 3-year follow-up study among primary care attenders aged 75 years and older. Age Ageing40, 456–463.
33.
PetersR, PetersJ, WarnerJ, BeckettN, BulpittC (2008) Alcohol, dementia and cognitive decline in the elderly: A systematic review. Age Ageing37, 505–512.
SaitoM, ChakrabortyG, MaoRF, PaikSM, VadaszC, SaitoM (2010) Tau phosphorylation and cleavage in ethanol-induced neurodegeneration in the developing mouse brain. Neurochem Res35, 651–659.
JoshiAU, Van WassenhoveLD, LogasKR, MinhasPS, AndreassonKI, WeinbergKI, ChenCH, Mochly-RosenD (2019) Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s disease related pathology. Acta Neuropathol Commun7, 190.
38.
VenkataramanA, KalkN, SewellG, RitchieCW, Lingford-HughesA (2017) Alcohol and Alzheimer’s disease-does alcohol dependence contribute to beta-amyloid deposition, neuroinflammation and neurodegeneration in Alzheimer’s disease?Alcohol Alcohol52, 151–158.
39.
ClarkeTK, AdamsMJ, DaviesG, HowardDM, HallLS, PadmanabhanS, MurrayAD, SmithBH, CampbellA, HaywardC, PorteousDJ, DearyIJ, McIntoshAM (2017) Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117). Mol Psychiatry22, 1376–1384.
JansenWJ, OssenkoppeleR, KnolDL, TijmsBM, ScheltensP, VerheyFR, VisserPJ, Amyloid Biomarker Study G, AaltenP, AarslandD, AlcoleaD, AlexanderM, AlmdahlIS, ArnoldSE, BaldeirasI, BarthelH, van BerckelBN, BibeauK, BlennowK, BrooksDJ, van BuchemMA, CamusV, CavedoE, ChenK, ChetelatG, CohenAD, DrzezgaA, EngelborghsS, FaganAM, FladbyT, FleisherAS, van der FlierWM, FordL, ForsterS, ForteaJ, FoskettN, FrederiksenKS, Freund-LeviY, FrisoniGB, FroelichL, GabryelewiczT, GillKD, GkatzimaO, Gomez-TortosaE, GordonMF, GrimmerT, HampelH, HausnerL, HellwigS, HerukkaSK, HildebrandtH, IshiharaL, IvanoiuA, JagustWJ, JohannsenP, KandimallaR, KapakiE, Klimkowicz-MrowiecA, KlunkWE, KohlerS, KoglinN, KornhuberJ, KrambergerMG, Van LaereK, LandauSM, LeeDY, de LeonM, LisettiV, LleoA, MadsenK, MaierW, MarcussonJ, MattssonN, de MendoncaA, MeulenbroekO, MeyerPT, MintunMA, MokV, MolinuevoJL, MollergardHM, MorrisJC, MroczkoB, Van der MusseleS, NaDL, NewbergA, NordbergA, NordlundA, NovakGP, ParaskevasGP, ParnettiL, PereraG, PetersO, PoppJ, PrabhakarS, RabinoviciGD, RamakersIH, RamiL, Resende de OliveiraC, RinneJO, RodrigueKM, Rodriguez-RodriguezE, RoeCM, RotU, RoweCC, RutherE, SabriO, Sanchez-JuanP, SantanaI, SarazinM, SchroderJ, SchutteC, SeoSW, SoeteweyF, SoininenH, SpiruL, StruyfsH, TeunissenCE, TsolakiM, VandenbergheR, VerbeekMM, VillemagneVL, VosSJ, van Waalwijk van DoornLJ, WaldemarG, WallinA, WallinAK, WiltfangJ, WolkDA, ZbochM, ZetterbergH (2015) Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA313, 1924–1938.
44.
WegmannS, BennettRE, DelormeL, RobbinsAB, HuM, McKenzieD, KirkMJ, SchiantarelliJ, TunioN, AmaralAC, FanZ, NichollsS, HudryE, HymanBT (2019) Experimental evidence for the age dependence of tau protein spread in the brain. Sci Adv5, eaaw6404.
