Abstract
INTRODUCTION
The presence of psychosis in Alzheimer’s disease (AD) is suggested to be associated with distinct molecular and neuropathological profiles in the brain.
METHODS
We assessed brain DNA methylation in AD donors with psychosis (AD+P) and without psychosis (AD−P) using the EPIC array. Weighted gene correlation network analysis identified modules of co-methylated genes in a discovery cohort (PITT-ADRC: N = 113 AD+P, N = 40 AD−P), with validation in an independent cohort (BDR: N = 79 AD+P, N = 117 AD−P), with Gene Ontology and cell-type enrichment analysis. Genetic data were integrated to identify methylation quantitative trait loci (mQTLs), which were co-localized with GWAS for related traits.
RESULTS
We replicated one AD+P associated module, which was enriched for synaptic pathways and in excitatory and inhibitory neurons. mQTLs in this module co-localized with variants associated with schizophrenia and educational attainment.
DISCUSSION
This represents the largest epigenetic study of AD+P to date, identifying pleiotropic relationships between AD+P and related traits.
Highlights
DNA methylation was assessed in the prefrontal cortex in subjects with AD+P and AD−P.
WGCNA identified six modules of co-methylated loci associated with AD+P in a discovery cohort.
One of the modules was replicated in an independent cohort.
This module was enriched for synaptic genes and in excitatory and inhibitory neurons.
mQTLs mapping to genes in the module co-localized with GWAS loci for schizophrenia and educational attainment.
If you do not see content above, kindly GO TO SOURCE.
Not all publishers encode content in a way that enables republishing at Neuro.vip.
This post is Copyright: Morteza Kouhsar,
Luke Weymouth,
Adam R. Smith,
Jennifer Imm,
Claudia Bredemeyer,
Yehani Wedatilake,
Ali Torkamani,
Sverre Bergh,
Geir Selbæk,
Jonathan Mill,
Clive Ballard,
Robert A. Sweet,
Julia Kofler,
Byron Creese,
Ehsan Pishva,
Katie Lunnon | February 12, 2025