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Updated: Aug 19, 2025

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

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Amyloid precursor protein and mitochondria

Taylor A Strope1, Heather M Wilkins2

  • 1University of Kansas Alzheimer's Disease Center, Kansas City, KS, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: https://twitter.com/OneDayDrTay.

Current Opinion in Neurobiology
|December 3, 2022
PubMed

Insights

Alzheimer's disease (AD) research shows amyloid precursor protein (APP) and its processing enzymes in mitochondria. This mitochondrial localization impacts cellular energy production and AD pathology.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is hallmarked by amyloid precursor protein (APP) to amyloid beta (Aβ) processing.
  • The amyloid cascade hypothesis for AD pathogenesis faces challenges due to recent therapeutic failures.
  • Metabolic deficits and mitochondrial dysfunction are consistently observed in AD patients.

Purpose of the Study:

  • To review evidence for APP and γ-secretase localization within mitochondria.
  • To discuss the functional implications of APP processing in the mitochondrial compartment.
  • To explore the role of APP and its metabolites in regulating mitochondrial function.

Main Methods:

  • Literature review of studies investigating APP and γ-secretase localization.
  • Analysis of research on mitochondrial APP processing.
  • Examination of the impact of APP cleavage products on mitochondrial bioenergetics.

Main Results:

  • Evidence supports the presence and activity of APP and γ-secretase within mitochondria.
  • Mitochondrial localization of APP affects mitochondrial function.
  • APP processing within mitochondria has implications for AD pathogenesis.

Conclusions:

  • APP and γ-secretase's presence in mitochondria is significant for AD pathology.
  • Mitochondrial APP processing represents a potential therapeutic target for Alzheimer's disease.
  • Further research into mitochondrial APP metabolism is warranted for AD treatment strategies.
Keywords:
Alzheimer's diseaseAmyloid precursor proteinBioenergeticsMitochondriaγ-secretase

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