Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer's disease.

Mitochondrial plaques develop in AD model mice due to impaired mitophagy and lysosomal dysfunction, with large accumulations of mitochondria forming in neuronal processes.

• Why it matters: Understanding the mechanisms behind mitochondrial accumulation and lysosomal failure in AD is crucial, as these contribute to disease pathology and may reveal new therapeutic targets.
• What they did: Researchers used APP/PSEN1/mt-Keima mice with a mitophagy reporter to observe mitochondrial buildup, lysosomal recruitment, and plaque formation, alongside analysis of 5xFAD mice and human AD brains.
• The result: Mitochondrial plaques, often co-occurring with amyloid, result from incomplete degradation due to lysosomal impairment, and their identification in multiple models suggests they are a novel pathological feature of AD.