期刊
ALZHEIMERS & DEMENTIA
卷 17, 期 10, 页码 1628-1640出版社
WILEY
DOI: 10.1002/alz.12330
关键词
Alzheimer' s disease; biomarker; cerebrospinal fluid; chitinase‐ 3‐ like protein 1; genome‐ wide association study; neurofilament light; neurogranin
资金
- European Union [115372]
- German Research Foundation [BE2287/7-1]
This study identified novel genetic associations between TMEM106B and NfL CSF levels, as well as between CPOX and YKL-40. The findings provide important insights into interindividual variation in AD-related CSF biomarkers, shedding light on the sequence of events in neuropathological processes relevant to AD.
Introduction 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. Methods 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. Results 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. Discussion 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.
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