Blood DNA methylation signatures to detect dementia prior to overt clinical symptoms

Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
Peter Daniel FransquetJoanne Ryan

Abstract

This study determined whether blood DNA methylation (DNAm) patterns differentiate individuals with presymptomatic dementia compared to controls. DNAm was measured in 73 individuals prior to dementia diagnosis and 87 cognitively healthy controls matched for age, sex, smoking, education, and baseline cognition. DNAm was also measured at 3 years follow-up in 25 dementia cases, and 24 controls. Cases and controls differed in DNAm (unadjusted P < .01) at the time of diagnosis (n = 28,787 probes), and pre-diagnosis (n = 15,111 probes), with cg01404610 (General transcription factor IIA subunit 1 gene) significant after correction for multiple testing. Overall, 1150 probes overlapped between analyses (methylation differences from -10.6% to +11.0%), and effect sizes increased from pre-diagnosis to diagnosis. Discernible blood DNAm signatures are in dementia cases before the appearance of overt clinical symptoms. Blood-based methylation may serve as a potential biomarker of dementia, but further investigation is needed to determine their true clinical utility.

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Citations

Mar 25, 2021·Acta Neuropathologica Communications·Vijay K RamananUNKNOWN Alzheimer’s Disease Neuroimaging Initiative (ADNI)

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Methods Mentioned

BETA
methylation profiling

Software Mentioned

Bioconductor
minfi R package
R
limma
DMRcate
missMethyl R
ASPREE
getSex
R package Minfi
R package “ limma

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