Epigenome-wide association study of cerebrospinal fluid-based biomarkers of Alzheimer's disease in cognitively normal individuals.

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: We conducted one of the largest (n = 735) blood DNA methylation (DNAm) studies of Alzheimer's disease cerebrospinal fluid (AD CSF) biomarkers. This is the first epigenome-wide association study in cognitively normal participants examining AD CSF biomarkers. Limited associations between blood DNAm and AD CSF biomarkers were identified.