TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels.
Alzheimer's disease
biomarker
cerebrospinal fluid
chitinase-3-like protein 1
genome-wide association study
neurofilament light
neurogranin
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
16
01
2021
received:
08
07
2020
accepted:
13
02
2021
pubmed:
16
5
2021
medline:
30
12
2021
entrez:
15
5
2021
Statut:
ppublish
Résumé
Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
Substances chimiques
Biomarkers
0
CHI3L1 protein, human
0
Chitinase-3-Like Protein 1
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Neurofilament Proteins
0
TMEM106B protein, human
0
neurofilament protein L
0
Neurogranin
132654-77-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1628-1640Subventions
Organisme : Alzheimer's Society
ID : 171
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17214
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Informations de copyright
© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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