TY - JOUR
T1 - Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers
AU - EADB consortium
AU - The GR@ACE study group
AU - Jansen, Iris E.
AU - van der Lee, Sven J.
AU - Gomez-Fonseca, Duber
AU - de Rojas, Itziar
AU - Dalmasso, Maria Carolina
AU - Grenier-Boley, Benjamin
AU - Zettergren, Anna
AU - Mishra, Aniket
AU - Ali, Muhammad
AU - Andrade, Victor
AU - Bellenguez, Céline
AU - Kleineidam, Luca
AU - Küçükali, Fahri
AU - Sung, Yun Ju
AU - Tesí, Niccolo
AU - Vromen, Ellen M.
AU - Wightman, Douglas P.
AU - Alcolea, Daniel
AU - Alegret, Montserrat
AU - Alvarez, Ignacio
AU - Amouyel, Philippe
AU - Athanasiu, Lavinia
AU - Bahrami, Shahram
AU - Bailly, Henri
AU - Belbin, Olivia
AU - Bergh, Sverre
AU - Bertram, Lars
AU - Biessels, Geert Jan
AU - Blennow, Kaj
AU - Blesa, Rafael
AU - Boada, Mercè
AU - Boland, Anne
AU - Buerger, Katharina
AU - Carracedo, Ángel
AU - Cervera-Carles, Laura
AU - Chene, Geneviève
AU - Claassen, Jurgen A.H.R.
AU - Debette, Stephanie
AU - Deleuze, Jean Francois
AU - de Deyn, Peter Paul
AU - Diehl-Schmid, Janine
AU - Djurovic, Srdjan
AU - Dols-Icardo, Oriol
AU - Dufouil, Carole
AU - Duron, Emmanuelle
AU - Düzel, Emrah
AU - Fladby, Tormod
AU - Fortea, Juan
AU - Frölich, Lutz
AU - Ruiz, Agustín
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Amyloid-beta
KW - Cerebrospinal fluid
KW - GWAS
KW - Tau
UR - https://www.scopus.com/pages/publications/85137914762
UR - https://www.scopus.com/pages/publications/85137914762#tab=citedBy
U2 - 10.1007/s00401-022-02454-z
DO - 10.1007/s00401-022-02454-z
M3 - Article
C2 - 36066633
AN - SCOPUS:85137914762
SN - 0001-6322
VL - 144
SP - 821
EP - 842
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 5
ER -