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

Mitochondrial plaques develop in neurons of AD models and human brains due to impaired lysosomal degradation, highlighting a new pathological feature in Alzheimer's disease.

• Why it matters: Understanding the mechanisms behind mitochondrial accumulation and lysosomal dysfunction is crucial because they contribute to neuronal damage and disease progression in AD, yet direct evidence and detailed insights have been limited.
• What they did: Researchers used AD model mice expressing a mitophagy reporter (APP/PSEN1/mt-Keima) to observe large mitochondrial accumulations called mitochondrial plaques, which form through abnormal buildup and delayed lysosomal recruitment, with incomplete degradation.
• The result: The presence of mitochondrial plaques in mouse models and human AD brains reveals a new pathological entity, offering potential targets for therapeutic intervention to improve mitochondrial clearance in AD.