1314-Genomic Instability in Neurodegenerative Disorders

Paper Talk · Jul 21, 2026 · 20m

This research identifies a universal mechanism of genetic instability that links three major neurodegenerative disorders: ALS, FTD, and Alzheimer’s disease. By using single-cell whole-genome sequencing, scientists discovered that neurons in these diseased brains accumulate an excessive number of somatic mutations, most notably a specific signature of 2-base-pair deletions. These mutations are caused by the malfunction of topoisomerase 1 (TOP1), an enzyme that becomes trapped on DNA during periods of high oxidative stress. This process leads to single-strand DNA breaks and eventual genome…