Long genes are more frequently affected by somatic mutations and show reduced expression in Alzheimer's disease: Implications for disease etiology
Publication year
2021Source
Alzheimer's & Dementia, 17, 3, (2021), pp. 489-499ISSN
Publication type
Article / Letter to editor
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Organization
Cognitive Neuroscience
PI Group Statistical Imaging Neuroscience
Geriatrics
Journal title
Alzheimer's & Dementia
Volume
vol. 17
Issue
iss. 3
Page start
p. 489
Page end
p. 499
Subject
220 Statistical Imaging Neuroscience; Radboudumc 1: Alzheimer`s disease DCMN: Donders Center for Medical Neuroscience; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical NeuroscienceAbstract
Aging, the greatest risk factor for Alzheimer's disease (AD), may lead to the accumulation of somatic mutations in neurons. We investigated whether somatic mutations, specifically in longer genes, are implicated in AD etiology. First, we modeled the theoretical likelihood of genes being affected by aging-induced somatic mutations, dependent on their length. We then tested this model and found that long genes are indeed more affected by somatic mutations and that their expression is more frequently reduced in AD brains. Furthermore, using gene-set enrichment analysis, we investigated the potential consequences of such long gene disruption. We found that long genes are involved in synaptic adhesion and other synaptic pathways that are predicted to be inhibited in the brains of AD patients. Taken together, our findings indicate that long gene-dependent synaptic impairment may contribute to AD pathogenesis.
This item appears in the following Collection(s)
- Academic publications [238441]
- Donders Centre for Cognitive Neuroimaging [3824]
- Electronic publications [122543]
- Faculty of Medical Sciences [90373]
- Open Access publications [97534]
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