Mitochondrial Dysfunction in Alzheimer's Disease: Opportunities for Drug Development

Alzheimer's disease (AD) is one of the major reasons for 60-80% cases of senile dementia occurring as a result of the accumulation of plaques and tangles in the hippocampal and cortical neurons of the brain leading to neurodegeneration and cell death. The other pathological features of AD comprise abnormal microvasculature, network abnormalities, interneuronal dysfunction, increased beta-amyloid production and reduced clearance, increased inflammatory response, elevated production of reactive oxygen species, impaired brain metabolism, hyperphosphorylation of tau, and disruption of acetylcholine signaling. Among all these pathologies, Mitochondrial Dysfunction (MD), regardless of it being an inciting insult or a consequence of the alterations, is related to all the associated AD pathologies. Observed altered mitochondrial morphology, distribution and movement, increased oxidative stress, dysregulation of enzymes involved in mitochondrial functioning, impaired brain metabolism, and impaired mitochondrial biogenesis in AD subjects suggest the involvement of mitochondrial malfunction in the progression of AD. Here, various pre-clinical and clinical evidence establishing MD as a key mediator in the progression of neurodegeneration in AD are reviewed and discussed with an aim to foster future MD based drug development research for the management of AD.

Automated summary

Alzheimer's disease is a major cause of senile dementia, characterized by accumulation of plaques and tangles in the brain leading to neurodegeneration and cell death, along with other pathological features such as abnormal microvasculature and increased beta-amyloid production. Mitochondrial Dysfunction (MD) is implicated in all associated AD pathologies, with evidence suggesting its involvement in the progression of neurodegeneration in AD.