Mitochondria and Alzheimer's disease: amyloid-β peptide uptake and degradation by the presequence protease, hPreP

Several lines of evidence suggest mitochondrial dysfunction as a possible underlying mechanism of Alzheimer's disease (AD). Accumulation of the amyloid-beta peptide (A beta), a neurotoxic peptide implicated in the pathogenesis of AD, has been detected in brain mitochondria of AD patients and AD transgenic mouse models. In vitro evidence suggests that the A beta causes mitochondrial dysfunction e.g. oxidative stress, mitochondrial fragmentation and decreased activity of cytochrome c oxidase and TCA cycle enzymes. Here we review the link between mitochondrial dysfunctions and AD. In particular we focus on the mechanism for A beta uptake by mitochondria and on the recently identified A beta degrading protease in human brain mitochondria.