Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1

阿尔茨海默病早期的昼夜节律改变与 BMAL1 中 DNA 甲基化的异常周期有关

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作者:Peter Cronin, Michael J McCarthy, Andrew S P Lim, David P Salmon, Douglas Galasko, Eliezer Masliah, Philip L De Jager, David A Bennett, Paula Desplats

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.

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.

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