Epigenome‐wide association study of cerebrospinal fluid–based biomarkers of Alzheimer's disease in cognitively normal individuals
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INTRODUCTION
Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are reliable predictors of future AD risk. We investigated whether pre‐clinical changes in AD CSF biomarkers are reflected in blood DNA methylation (DNAm) levels in cognitively normal participants.
METHODS
We profiled blood‐based DNAm with the EPIC array in participants without a diagnosis of cognitive impairment in the Emory Healthy Brain Study (EHBS; N = 495), Alzheimer's Disease Neuroimaging Initiative ( N = 122), and Parkinson's Progression Markers Initiative ( N = 118) cohorts. Their CSF amyloid beta 42, total tau (t‐tau), and phosphorylated tau181 levels were quantified using Elecsys immunoassays. We conducted epigenome‐wide association studies to assess associations between DNAm and CSF biomarkers of AD.
RESULTS
In EHBS, no loci were Bonferroni significant after adjusting for confounding factors. In the meta‐analysis of all three cohorts, DNAm in cg22976567 ( LMNA ) was significantly associated with higher CSF t‐tau levels.
DISCUSSION
Our study showed little evidence of an association between differential blood‐based DNAm and pre‐clinical AD CSF biomarkers.
Highlights
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We conducted one of the largest ( n = 735) blood DNA methylation (DNAm) studies of Alzheimer's disease cerebrospinal fluid (AD CSF) biomarkers.
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This is the first epigenome‐wide association study in cognitively normal participants examining AD CSF biomarkers.
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Limited associations between blood DNAm and AD CSF biomarkers were identified.
