Mitochondrial dysfunction in Alzheimer’s disease

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive decline and distinct neuropathological features. The absence of a definitive cure presents a significant challenge in neurology and neuroscience. Early clinical manifestations, such as memory retrieval deficits and apathy, underscore the need for a deeper understanding of the disease's underlying mechanisms. While amyloid-β plaques and tau neurofibrillary tangles have dominated research efforts, accumulating evidence highlights mitochondrial dysfunction as a central factor in AD pathogenesis. Mitochondria, essential cellular organelles responsible for energy production necessary for neuronal function become impaired in AD, triggering several cellular consequences. Factors such as oxidative stress, disturbances in energy metabolism, failures in the mitochondrial quality control system, and dysregulation of calcium release are associated with mitochondrial dysfunction. These abnormalities are closely linked to the neurodegenerative processes driving AD development and progression. This review explores the intricate relationship between mitochondrial dysfunction and AD pathogenesis, emphasizing its role in disease onset and progression, while also considering its potential as a biomarker and a therapeutic target. Fig. 1: Graphic Abstract. Summary of main points discussed in the article. Created in https://BioRender.com • Dysfunctional mitochondria have been implicated in the pathogenesis of Alzheimer’s disease. • Mitochondrial homeostasis is necessary for cell energy production, calcium equilibrium and apoptotic signaling. • Mitochondria dysfunction leads to altered electron transport chain function, free radical generation and oxidative stress. • Mitochondria are emerging as biomarkers for early detection and monitoring of Alzheimer’s disease progression. • Therapeutic targeting of mitochondrial dysfunction offers a novel approach against Alzheimer’s disease.