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Brain 5-hydroxymethylcytosine alterations are associated with Alzheimer’s disease neuropathology
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Brain 5-hydroxymethylcytosine alterations are associated with Alzheimer’s disease neuropathology
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Journal Article
Brain 5-hydroxymethylcytosine alterations are associated with Alzheimer’s disease neuropathology
2025
Overview
5-hydroxymethylcytosine, also known as the sixth DNA base of the genome, plays an important role in brain aging and neurological disorders such as Alzheimer’s disease. However, little is known about its genome-wide distribution and its association with Alzheimer’s disease pathology. Here, we report a genome-wide profiling of 5-hydroxymethylcytosine in 1079 autopsied brains (dorsolateral prefrontal cortex) of older individuals and assess its association with multiple measures of Alzheimer’s disease pathologies, including pathological diagnosis of Alzheimer’s disease, amyloid-β load, and PHFtau tangle density. Of 197,765 5-hydroxymethylcytosine regions detected, we identified 2821 differentially hydroxymethylated regions associated with Alzheimer’s disease neuropathology after controlling for multiple testing and covariates. Many differentially hydroxymethylated regions are located within known Alzheimer’s disease loci, such as
RIN3, PLCG2, ITGA2B
, and
USP6NL
. Integrative multi-omics analyses support a potential mechanistic role of 5-hydroxymethylcytosine alterations in Alzheimer’s disease. Our study presents a large-scale genome-wide atlas of 5-hydroxymethylcytosine in Alzheimer’s brain and offers insight into the mechanism underlying Alzheimer’s disease pathogenesis.
5-hydroxymethylcytosine, the sixth DNA base, plays a key role in brain aging and Alzheimer’s disease. Here, the authors study over 1000 deceased brains to identify genes with 5-hydroxymethylcytosine alterations linked to Alzheimer’s pathology.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/43
/ 5-Methylcytosine - analogs & derivatives
/ 5-Methylcytosine - metabolism
/ Aged
/ Aging
/ Alzheimer Disease - genetics
/ Alzheimer Disease - metabolism
/ Alzheimer Disease - pathology
/ Amyloid beta-Peptides - metabolism
/ Brain
/ DNA
/ Female
/ Genome-Wide Association Study
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Male
/ Prefrontal Cortex - metabolism
/ Prefrontal Cortex - pathology
/ Science
