TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels

Alzheimer’s Disease Neuroimaging Initiative (ADNI)

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAlzheimer's and Dementia
Volume17
Issue number10
Pages (from-to)1628-1640
Number of pages13
ISSN1552-5260
DOIs
Publication statusPublished - Oct 2021

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

Fingerprint

Dive into the research topics of 'TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels'. Together they form a unique fingerprint.

Cite this