Insights into amyloid-β-induced mitochondrial dysfunction in Alzheimer disease

Amyloid-β has long been implicated in the pathogenesis of Alzheimer disease. The focus was initially on the extracellular fibrillar deposits of amyloid-β but more recently has shifted to intracellular oligomeric forms of amyloid-β. Unfortunately, the mechanism(s) by which either extracellular or intracellular amyloid-β induces neuronal toxicity remains unclear. That said, a number of recent studies indicate that mitochondria might be an important target of amyloid-β. Neurons rely heavily on mitochondria for energy and it is well established that mitochondrial dysfunction might be an important target of amyloid-β. Mechanistically, amyloid-β aggregates in mitochondria to impair function, leading to energy hypometabolism and elevated reactive oxygen species production. Additionally, amyloid-β affects the balance of mitochondrial fission/fusion and mitochondrial transport, negatively impacting a host of cellular functions of neurons. Here, we review the role that amyloid-β plays in mitochondrial structure and function of neurons and the importance of this in the pathogenesis of Alzheimer disease.