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The Neuroscientist
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Amyloid Precursor Protein and Mitochondrial Dysfunction in Alzheimer's Disease

Hindupur K. Anandatheerthavarada

Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, ann1234{at}vet.upenn.edu

Latha Devi

Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia

Growing evidence suggests that mitochondrial dysfunction is one of the key intracellular lesions associated with the pathogenesis of Alzheimer's disease (AD). Mitochondria, the powerhouses of the cell, participate in a number of physiological functions that include calcium homeostasis, signal transduction, and apoptosis. However, the pathophysiological mechanisms underlying the decline of mitochondrial vital functions leading to the dysfunction of mitochondria during AD are not well understood. Recent literature has observed the accumulation of Alzheimer's amyloid precursor protein (APP) and its C-terminal—cleaved product ß-amyloid (Aß) in the mitochondrial compartment. Furthermore, evidence also implicates that the accumulation of full-length APP and Aß in the mitochondrial compartment has a causative role in impairing mitochondrial physiological functions. Here, we review the mode of mitochondrial transport of full-length APP and Aß and its pathological implications in bringing about mitochondrial dysfunction as seen in AD. NEUROSCIENTIST 13(6):626—638, 2007. DOI: 10.1177/1073858407303536

Key Words: Alzheimer's disease • Mitochondrial dysfunction • Amyloid precursor protein • Aß • Acidic domain • Mitochondria • Translocational arrest • Import channels • Transgenic mouse models

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This version was published on December 1, 2007

The Neuroscientist, Vol. 13, No. 6, 626-638 (2007)
DOI: 10.1177/1073858407303536
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