Biology subjects

Bergmann, P. E.

Publications and source records attributed to Bergmann, P. E..

4 recordsLinked to original sources

bioRxiv2025

Epigenetic genes are differentially methylated in the blood of persons with mild cognitive impairment and Alzheimers disease

BackgroundEnvironmental factors play a role in AD pathology and are mediated by changes in DNA methylation levels. Methods and ResultsWe investigated whole genome methylation sequencing (WGMS) data from the blood of participants with mild cognitive impairment (MCI, N=99), late onset dementia due to Alzheimers disease (AD, N=109), and who are cognitively unimpaired (CU, N=174) to test for differential methylation in 812 genes with roles in epigenetic regulation (e.g., DNA methylation and demethylation, chromatin remodeling, histone modification, and RNA modification) curated from the EpiFactors 2.1 database. 71/812 genes were differentially methylated comprising 190 unique differentially methylated positions (DMPs) in MCI (MCI vs. CU pairwise comparison). 60/812 genes were differentially methylated comprising 220 DMPs in AD (AD vs. CU pairwise comparison). The majority of differentially methylated genes in both MCI (41/71) and AD (33/60) were histone modification genes and 23 differentially methylated genes were shared in both pairwise comparisons. 96 genes were differentially methylated comprising 243 DMPs between persons with MCI and AD (AD vs. MCI pairwise comparison). 10 differentially methylated genes were shared between the 3 pairwise comparisons, including CUGBP elav-like family member 2 (CELF2), histone deacetylase 9 (HDAC9), RNA binding fox-1 homolog 1 (RBFOX1), TATA-box binding protein associated factor 4 (TAF4), and thymine DNA glycosylase (TDG). ConclusionGenes that participate in the epigenetic regulation of gene expression, particularly histone modifications, are differentially methylated in blood between persons with and without MCI and AD, warranting further elucidation of their role in the molecular pathogenesis of cognitive decline.

genomics↗

bioRxiv2025

Differential DNA methylation in blood in nuclear genes that encode mitochondrial proteins in mild cognitive impairment and Alzheimers disease

BackgroundAltered mitochondrial function contributes to the pathogenesis of mild cognitive impairment (MCI) and late-onset dementia due to Alzheimers disease (AD). ObjectiveTo test for differential methylation in nuclear genes that encode proteins that participate in mitochondrial function between cognitively unimpaired participants (CU) and those with MCI and AD. MethodsRecently published whole genome methylation sequencing (WGMS) in blood from CU participants (N=174), and those with MCI (N=99) and AD (N=109) was used to test for differential methylation in 1,121 nuclear genes that encode proteins that participate in mitochondrial function in the Human Protein Atlas. ResultsSeventy-four nuclear genes that encode proteins that participate in mitochondrial function were differentially methylated between persons with MCI and CU. Seventy-one genes were differentially methylated between persons with AD and CU, and 132 genes were differentially methylated between persons with MCI and AD. Thirteen differentially methylated genes shared between the 3 comparisons support contributions from disrupted metabolism and oxidative stress pathways in AD pathogenesis. ConclusionsNuclear genes that encode proteins that participate in mitochondrial glucose metabolism, fatty acid metabolism and oxidative stress pathways are differentially methylated between persons who are CU and those with MCI and AD.

genomics↗

bioRxiv2025

Sex-Specific Differential DNA Methylation in Mild Cognitive Impairment and Alzheimers Disease

Sex differences in late-onset Alzheimers disease (AD) progression include accelerated decrements in cognitive status and greater amyloid and tau biomarker burdens in females. To identify sex-specific differentially methylated positions (DMPs) and genes in persons with mild cognitive impairment (MCI) and AD, we analyzed whole genome methylation sequencing on blood samples from participants with MCI (N=99, 52% female), AD (N=109, 43% female), and those cognitively unimpaired (CU; N=174, 52% female). Ninety-four percent of DMPs from MCI vs. CU, AD vs. CU, and AD vs. MCI pairwise comparisons were sex-specific. Female-specific DMPs were enriched in neurologic gene sets (e.g., synaptic membrane, ion channel complex), while male-specific DMPs showed limited enrichment. Sex-specific DMPs overlapped blood-specific enhancers, promoters, and transcription factor binding motifs, highlighting divergent epigenetic regulation by sex. These findings identify sex-specific genes and molecular pathways in MCI and AD and support that blood DNA methylation levels can distinguish cognitive status.

genomics↗

bioRxiv2024

Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status

INTRODUCTIONWhole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimers disease (AD) but has not been tested in persons with mild cognitive impairment (MCI). METHODSWe used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU). RESULTSWGMS identified 9,756 differentially methylated positions (DMPs) in persons with MCI, including 1,743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport. 447 DMPs exhibit progressively increasing or decreasing DNA methylation levels between CU, MCI, and AD that correspond to cognitive status. DISCUSSIONWGMS identifies DMPs in known and newly detected genes in blood from persons with MCI and AD that support blood DNA methylation levels as candidate biomarkers of cognitive status.

genomics↗