Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
Iris E JansenSven J Van der LeeDuber Gomez-FonsecaItziar De RojasMaria Carolina DalmassoBenjamin Grenier-BoleyAnna ZettergrenAniket MishraMuhammad AliVictor AndradeCéline BellenguezLuca KleineidamFahri KüçükaliYun Ju SungNiccolo TesíEleonora M VromenDouglas P WightmanDaniel AlcoleaMontserrat AlegretIgnacio AlvarezPhilippe AmouyelLavinia AthanasiuShahram BahramiHenri BaillyOlivia BelbinSverre BerghLars BertramGeert Jan BiesselsKaj BlennowRafael BlesaMercè BoadaAnne BolandKatharina BuergerÁngel CarracedoLaura Cervera-CarlesGeneviève CheneJurgen A H R ClaassenStephanie DebetteJean-Francois DeleuzePeter Paul de DeynJanine Diehl-SchmidSrdjan DjurovicOriol Dols-IcardoCarole DufouilEmmanuelle DuronEmrah Düzelnull nullTormod FladbyJuan ForteaLutz FrölichPablo García GonzálezMaria Garcia-MartinezIna GieglingOliver GoldhardtJohan GobomTimo GrimmerAnnakaisa HaapasaloHarald HampelOlivier HanonLucrezia HausnerStefanie Heilmann-HeimbachSeppo HelisalmiMichael T HenekaIsabel HernándezSanna-Kaisa HerukkaHenne HolstegeJonas JarholmSilke KernAnne-Brita KnapskogAnne M KoivistoKornhuber JohannesTeemu KuulasmaaCarmen LageChristoph LaskeVille LeinonenLewczuk PiotrAlberto LleóAdolfo López de MunainSara Lopez-GarciaWolfgang MaierMarta MarquiéMerel O MolLaura MontrrealFermin MorenoSonia Moreno-GrauGael NicolasMarkus M NöthenAdelina OrellanaLene PålhaugenJanne M PapmaFlorence PasquierRobert PerneczkyOliver PetersYolande A L PijnenburgJulius PoppDanielle PosthumaAna PozuetaJosef PrillerRaquel PuertaInés QuintelaInez RamakersEloy Rodríguez-RodríguezDan RujescuIngvild SaltvedtPascual Sánchez JuanPhilip ScheltensNorbert ScherbaumMatthias SchmidAnja SchneiderGeir SelbaekPer SelnesAlexey ShadrinIngmar SkoogHilkka SoininenLluís TárragaStefan Teipelnull nullBetty M TijmsMagda TsolakiChristine Van BroeckhovenJasper Van DongenJohn C van SwietenRik VandenbergheJean-Sébastien VidalPieter J VisserJonathan VogelgsangMargda WaernMichael WagnerJens WiltfangMandy M J WittensHenrik ZetterbergMiren ZulaicaCornelia M Van DuijnMaria BjerkeSebastiaan EngelborghsFrank JessenCharlotte E TeunissenPau PastorMikko HiltunenMartin IngelssonOle Andreas AndreassenJordi ClarimónKristel SleegersAgustín RuizAlfredo RamirezCruchaga CarlosJean-Charles LambertWiesje Maria van der FlierPublished in: Acta neuropathologica (2022)
Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
Keyphrases
- cerebrospinal fluid
- genome wide
- genome wide association study
- cognitive decline
- dna methylation
- systematic review
- mild cognitive impairment
- copy number
- heart failure
- left ventricular
- single cell
- small molecule
- high throughput
- randomized controlled trial
- quality improvement
- catheter ablation
- meta analyses
- white matter
- rna seq
- gene expression
- skeletal muscle
- metabolic syndrome
- adipose tissue
- protein protein
- insulin resistance
- subarachnoid hemorrhage
- drug induced