Somatic mutations in neurodegeneration: from detection to disease mechanisms
Abstract
Somatic mutations are postzygotic DNA alterations that accumulate throughout development and aging, underlying somatic mosaicism across cell populations. Neurons are particularly vulnerable due to oxidative stress, high metabolic demand, and age-related decline in DNA damage response pathways, promoting cell-type-specific dysfunction. Somatic repeat instability is an established driver in Huntington’s disease, yet the extent and functional impact of somatic mutagenesis in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis remains unresolved. This article highlights how advances in single-cell and single-molecule sequencing, integrated with computational and machine learning approaches, support detecting ultra-rare variants and establishing causal links between somatic mutagenesis and neurodegeneration.
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BibTeX
@article{piaszykborychowska2026somatic,
title = {{Somatic mutations in neurodegeneration: from detection to disease mechanisms}},
author = {Anna Piaszyk-Borychowska and Weronika Śliwińska and Marta Olejniczak},
journal = {BMC Biology},
year = {2026},
month = nov,
doi = {10.1186/s12915-026-02778-2},
url = {https://link.springer.com/article/10.1186/s12915-026-02778-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Somatic mutations in neurodegeneration: from detection to disease mechanisms
AU - Anna Piaszyk-Borychowska
AU - Weronika Śliwińska
AU - Marta Olejniczak
PY - 2026
DA - 2026/11/05
JO - BMC Biology
DO - 10.1186/s12915-026-02778-2
UR - https://link.springer.com/article/10.1186/s12915-026-02778-2
AB - Somatic mutations are postzygotic DNA alterations that accumulate throughout development and aging, underlying somatic mosaicism across cell populations. Neurons are particularly vulnerable due to oxidative stress, high metabolic demand, and age-related decline in DNA damage response pathways, promoting cell-type-specific dysfunction. Somatic repeat instability is an established driver in Huntington’s disease, yet the extent and functional impact of somatic mutagenesis in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis remains unresolved. This article highlights how advances in single-cell and single-molecule sequencing, integrated with computational and machine learning approaches, support detecting ultra-rare variants and establishing causal links between somatic mutagenesis and neurodegeneration.
SN - 1741-7007
ER -