TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels.
Details
Serval ID
serval:BIB_CA4AD3F89C29
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels.
Journal
Alzheimer's & dementia
Working group(s)
Alzheimer's Disease Neuroimaging Initiative (ADNI)
ISSN
1552-5279 (Electronic)
ISSN-L
1552-5260
Publication state
Published
Issued date
10/2021
Peer-reviewed
Oui
Volume
17
Number
10
Pages
1628-1640
Language
english
Notes
Publication types: 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.
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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.
Keywords
Aged, Alzheimer Disease/genetics, Biomarkers/cerebrospinal fluid, Chitinase-3-Like Protein 1/genetics, Female, Genome-Wide Association Study, Humans, Male, Membrane Proteins/genetics, Nerve Tissue Proteins/genetics, Neurofilament Proteins/genetics, Neurogranin/cerebrospinal fluid, Alzheimer's disease, biomarker, cerebrospinal fluid, chitinase-3-like protein 1, genome-wide association study, neurofilament light, neurogranin
Pubmed
Web of science
Open Access
Yes
Create date
25/05/2021 14:52
Last modification date
05/01/2022 7:36