Biology subjects

Hogan, K. J.

Publications and source records attributed to Hogan, K. J..

6 recordsLinked to original sources

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↗

bioRxiv2024

Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study

ObjectiveAccelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults. MethodsThis study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA. ResultsNested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age. DiscussionSmall sample size limited estimate precision, however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.

neuroscience↗

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↗

bioRxiv2018

Longitudinal plasma metabolomics of aging and sex

Understanding how metabolites are longitudinally influenced by age and sex could facilitate the identification of metabolomic profiles and trajectories that indicate disease risk. We investigated the metabolomics of age and sex using longitudinal plasma samples from the Wisconsin Registry for Alzheimers Prevention (WRAP), a cohort of participants who were dementia free at enrollment. Metabolomic profiles were quantified for 2,316 fasting plasma samples among 1,187 participants, each with up to three study visits. Of 1,097 metabolites tested, 608 (55.4%) were associated with age and 680 (62.0%) with sex after correcting for multiple testing. Approximately twice as many metabolites were associated with age in stratified analyses of women versus men, and 63 metabolite trajectories significantly differed by sex, most notably including sphingolipids, which tended to increase in women and decrease in men with age. Using genome-wide genotyping, we also report the heritabilities of metabolites investigated, which ranged dramatically (0.2-99.2%); however, the median heritability of 36.2% suggests that many metabolites are highly influenced by a complex combination of genomic and environmental influences. These findings offer a more profound description of the aging process and may inform many new hypotheses regarding the role metabolites play in healthy and accelerated aging.

molecular biology↗

bioRxiv2018

Metabolites associated with early cognitive changes implicated in Alzheimer’s disease

We investigated the metabolomics of early cognitive changes related to Alzheimers disease (AD) in order to better understand mechanisms that could contribute to early stages and progression of this disease. This investigation used longitudinal plasma samples from the Wisconsin Registry for Alzheimers Prevention (WRAP), a cohort of participants who were dementia free at enrollment and enriched with a parental history of AD. Metabolomic profiles were quantified for 2,338 fasting plasma samples among 1,206 participants, each with up to three study visits. Of 1,097 metabolites tested, levels of seven were associated with executive function trajectories, including an amino acid and three fatty acids, but none were associated with delayed recall trajectories. Our time-varying metabolomic results suggest potential mechanisms that could contribute to the earliest signs of cognitive decline. In particular, fatty acids may be associated with cognition in a manner that is more complex than previously suspected.

neuroscience↗

bioRxiv2017

The Wisconsin Registry for Alzheimer’s Prevention: A Review of findings and current directions

The Wisconsin Registry for Alzheimers Prevention (WRAP) is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimers Disease (AD) dementia. Since late 2001, WRAP has enrolled 1,561 people at a mean baseline age of 54. Participants return for a second visit four years after baseline and subsequent visits occur every two years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up. Serially assessed cognition, self-reported medical and lifestyle histories (e.g. diet, physical and cognitive activity, sleep, and mood), laboratory tests, genetics, and linked studies comprising molecular imaging, structural imaging and cerebrospinal fluid data, have yielded many important findings. In this cohort, PH of probable AD is associated with 46% APOE {varepsilon}4 positivity, more than twice the rate of 22% among persons without PH. Subclinical or worse cognitive decline relative to internal normative data has been observed in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau positivity. Biomarker elevations, but not APOE or PH status, are associated with cognitive decline. Salutary health and lifestyle factors are associated with better cognition and brain structure, and lower AD pathophysiologic burden. Of paramount importance is establishing the amyloid and tau AD endophenotypes to which cognitive outcomes can be linked. Such data will provide new knowledge on the early temporal course of AD pathophysiology and inform the design of secondary prevention clinical trials.

neuroscience↗