Amyloid precursor protein and mitochondria

Amyloid Precursor Protein (APP) processing to amyloid beta (Ab) is a major hallmark of Alzheimer's disease (AD). The amyloid cascade hypothesis postulates that Ab accumulation and aggregation causes AD, however many therapeutics targeting Ab have failed recently. Decades of research describe metabolic deficits in AD. Mitochondrial dysfunction is observed in AD subjects within the brain and systemically. APP and g-secretase are localized to mitochondria. APP can be processed within mitochondria and its localization to mito-chondria affects function. Here we discuss the evidence showing APP and g-secretase localize to mitochondria. We also discuss the implications for the function of APP and its cleavage products in regulating mitochondrial function.

Automated summary

Processing of Amyloid Precursor Protein (APP) to amyloid beta (Ab) is a key characteristic of Alzheimer's disease (AD). The accumulation and aggregation of Ab is believed to cause AD, but recent attempts to target Ab therapeutically have been unsuccessful. Research has also evidenced metabolic deficits and mitochondrial dysfunction in AD, with localization of APP and γ-secretase to mitochondria. This article explores the evidence of the mitochondrial localization of APP and γ-secretase, and discusses their implications in regulating mitochondrial function.