Abnormal mitochondrial dynamics in Alzheimer disease

Abstract

Mitochondrial dysfunction is a prominent and early feature of Alzheimer disease, although the cause is unclear. Nonetheless, emerging evidence suggest that mitochondrial function is dependent on the dynamic balance of fission and fusion events. While an impaired balance of mitochondria fission and fusion is being increasingly implicated in neurodegenerative diseases, few studies have examined this aspect in AD. To address this issue, in this study, we investigated mitochondria morphology and distribution in biopsy brains from normal subjects and those from AD patients. We found disease‐related changes in mitochondrial morphology and distribution as well as changes in expression levels and distribution of mitochondrial fission and fusion proteins. To understand the underlying mechanisms of these mitochondria alterations in AD, we overexpressed or knocked down functional DLP1 and other mitochondrial proteins in rat primary neurons. Interestingly, in situations where functional protein changes mimicking that in AD, we found similar changes in mitochondrial morphology and distribution to that observed in AD neurons. We further demonstrated that elevated oxidative stress and increased amyloid‐β production are likely the potential pathogenic factors that cause impaired balance of mitochondrial fission/fusion.