Role of mitochondrial homeostasis and dynamics in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects a staggering percentage of the aging population and causes memory loss and cognitive decline. Mitochondrial abnormalities can be observed systemically and in brains of patients suffering from AD, and may account for part of the disease phenotype. In this review, we summarize some of the key findings that indicate mitochondrial dysfunction is present in AD-affected subjects, including cytochrome oxidase deficiency, endophenotype data, and altered mitochondrial morphology. Special attention is given to recently described perturbations in mitochondrial autophagy, fission–fusion dynamics, and biogenesis. We also briefly discuss how mitochondrial dysfunction may influence amyloidosis in Alzheimer's disease, why mitochondria are a valid therapeutic target, and strategies for addressing AD-specific mitochondrial dysfunction.

► Alzheimer's disease patients have systemic mitochondrial dysfunction.
► Mitochondrial dysfunction in Alzheimer's disease may drive other pathologies.
► Mitochondrial autophagy, fission, fusion, and biogenesis are altered in Alzheimer's.
► Mitochondria represent a reasonable Alzheimer's disease therapeutic target.