Mitochondrial translocation of amyloid precursor protein and its cleaved products: Relevance to mitochondrial dysfunction in Alzheimer's disease

Alzheimer.'s disease (AD) is a multifactorial disorder. Mitochondrial dysfunction is one of the key characteristics of AD pathogenesis. However, the mechanisms underlying the progression of mitochondrial impairment during AD are not clear. Growing evidence suggests a causative role for intracellular accumulation of amyloid precursor protein (APP) and its proteolytic products in the pathogenesis of AD. Furthermore, APP possesses several domains including a mitochondrial targeting sequence. Recent literature suggests that mitochondrial localization of full length APP and its C-terminal proteolytically cleaved derivative beta amyloid (A beta) are associated with the mitochondrial dysfunction. Here, we review the nature of mitochondrial localization of APP and A beta and their pathological implications in AD mitochondrial dysfunction.