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Updated: Jul 16, 2026
11:19
Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)
Published on: September 26, 2015
DNA methylation variability in Alzheimer's disease
Zhiguang Huo1, Yun Zhu2, Lei Yu3
1Department of Biostatistics, University of Florida, Gainesville, FL, USA.
Neurobiology of Aging
|January 20, 2019
Summary
DNA methylation instability, not just average levels, is linked to Alzheimer's disease (AD) brain changes. This variability in DNA methylation may influence AD susceptibility and neuropathology.
Area of Science:
- Neuroscience
- Epigenetics
- Genomics
Background:
- DNA methylation is crucial for brain aging and Alzheimer's disease (AD).
- Previous research primarily examined average DNA methylation, overlooking its variability.
- DNA methylation instability, or variability, may impact AD susceptibility.
Purpose of the Study:
- To investigate the role of DNA methylation variability in Alzheimer's disease neuropathology.
- To identify specific regions of variable DNA methylation associated with AD hallmarks.
Main Methods:
- Utilized DNA methylation data from the Religious Orders Study and Rush Memory and Aging Project.
- Identified variably methylated probes (VMPs) associated with amyloid-β and neurofibrillary tangles.
- Analyzed VMP clustering and overlap with differentially methylated probes.
Main Results:
- Discovered 249 VMPs linked to amyloid-β and 115 VMPs linked to neurofibrillary tangles.
- These VMPs formed 133 and 14 distinct regions, respectively.
- Most identified VMPs did not overlap with previously identified differentially methylated probes.
Conclusions:
- DNA methylation instability is a significant factor in AD neuropathology.
- Variably methylated probes capture distinct genetic sets relevant to AD pathology compared to differentially methylated probes.
- Emphasizes the importance of assessing DNA methylation variability in epigenetic studies of AD.
Keywords:
Alzheimer's diseaseAmyloid-β plaquesDNA methylation variabilityPFCPHF-tau tanglesPostmortem brainROSMAPMore Related Videos
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