Blood DNA methylation signatures to detect dementia prior to overt clinical symptoms. Issue 1 (9th July 2020)

• Record Type: Journal Article
• Authors: Fransquet, Peter Daniel; Lacaze, Paul; Saffery, Richard; Phung, James; Parker, Emily; Shah, Raj; Murray, Anne; Woods, Robyn L.; Ryan, Joanne
• Is Part Of: Alzheimer's & dementia. Volume 12:Issue 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-07-09
• Subjects: biomarker -- dementia -- epigenome‐wide association study -- methylation -- pre‐diagnosis; Alzheimer's disease -- Periodicals; Alzheimer's disease -- Diagnosis -- Periodicals; Dementia -- Periodicals; Dementia -- Diagnosis -- Periodicals; 616.831
• DOI: 10.1002/dad2.12056
• Languages: English
• ISSNs: 2352-8729

Abstract

Abstract: Introduction: This study determined whether blood DNA methylation (DNAm) patterns differentiate individuals with presymptomatic dementia compared to controls. Methods: 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. Results: 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. Discussion: 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.