The breaking point where repeat expansion triggers neuronal collapse in Huntington's disease

Cell Genom. 2025 Mar 12;5(3):100816. doi: 10.1016/j.xgen.2025.100816.

ABSTRACT

Somatic CAG expansion drives neuronal loss in Huntington's disease (HD), but how expansion results in pathogenesis has remained unclear. Handsaker et al.¹ use single-cell RNA and repeat length sequencing to reveal a phased model of expansion and toxicity, highlighting a critical tipping point beyond 150 CAG repeats where neuronal identity collapses and cells die.

PMID:40081335 | DOI:10.1016/j.xgen.2025.100816