Mitochondrial double-stranded RNA accumulation in brain aging and Alzheimer's disease.

ABSTRACT: Mitochondria and inflammation are tightly linked in aging and Alzheimer's disease (AD), and recent evidence implicates mitochondrial double-stranded RNA (mt-dsRNA) as a potential trigger of inflammation. We examined mt-dsRNA accumulation and dsRNA signaling in brain aging and AD using human brain tissue and complementary in vitro transcriptomic datasets, quantifying mitochondrial transcripts and dsRNA editing. We found that mt-dsRNA accumulated after midlife and coincided with reduced expression of mitochondrial RNA processing and translation machinery, along with increased expression of dsRNA antiviral signaling proteins, consistent with cytoplasmic mt-dsRNA-driven inflammation. In AD brains, mt-dsRNA accumulation was further increased and correlated with cognitive impairment, neur

SUBMITTER: Doser RL 

PROVIDER: S-EPMC12889667 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature