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Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1
Author(s) -
Cronin Peter,
McCarthy Michael J.,
Lim Andrew S.P.,
Salmon David P.,
Galasko Douglas,
Masliah Eliezer,
De Jager Philip L.,
Bennett David A.,
Desplats Paula
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.10.003
Subject(s) - dna methylation , circadian rhythm , biology , epigenetics , circadian clock , neurodegeneration , methylation , clock , genetics , microbiology and biotechnology , medicine , endocrinology , gene expression , gene , disease
Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, and neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and changes in DNA methylation have been reported in AD brains, but the pathways that mediate circadian deregulation in AD are incompletely understood. We hypothesized that aberrant DNA methylation may affect circadian rhythms in AD. Methods We investigated DNA methylation, transcription, and expression of BMAL1 , a positive regulator of the circadian clock, in cultured fibroblasts and brain samples from two independent cohorts of aging and AD. Results DNA methylation modulated rhythmic expression of clock genes in cultured fibroblasts. Moreover, rhythmic methylation of BMAL1 was altered in AD brains and fibroblasts and correlated with transcription cycles. Discussion Our results indicate that cycles of DNA methylation contribute to the regulation of BMAL1 rhythms in the brain. Hence, aberrant epigenetic patterns may be linked to circadian alterations in AD.