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Updated: Jul 10, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

Pathogenic role of mitochondrial [correction of mitochondral] amyloid-beta peptide

John Xi Chen1, Shi Du Yan

  • 1Harvey Cushing Institutes of Neuroscience, North Shore-Long Island Jewish Health System, Great Neck, NY 11021, USA. jchen1@nshs.edu

Expert Review of Neurotherapeutics
|November 14, 2007
PubMed

Insights

Alzheimer's disease (AD) involves brain metabolic dysfunction. Amyloid-beta (Abeta) peptide accumulates in mitochondria, interacting with ABAD to cause dysfunction, a potential therapeutic target for AD.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Metabolic dysfunction is an early hallmark of Alzheimer's disease (AD) brain.
  • Amyloid-beta peptide (Abeta) accumulation in neuritic plaques is implicated in AD pathogenesis.
  • The precise pathogenic role of Abeta, particularly within mitochondria, requires further elucidation.

Purpose of the Study:

  • To review the role of Abeta accumulation within mitochondria in Alzheimer's disease.
  • To investigate the interaction between Abeta and mitochondrial Abeta-binding alcohol dehydrogenase (ABAD).
  • To explore the potential of targeting Abeta-ABAD interaction for AD therapeutics.

Main Methods:

  • Review of studies on transgenic mouse models overexpressing mutant Abeta precursor protein.
  • Analysis of autopsied brain samples from Alzheimer's disease patients.
  • Examination of Abeta's interaction with ABAD and its downstream effects on mitochondrial function.

Main Results:

  • Progressive Abeta accumulation observed within mitochondria in both AD models and patients.
  • Abeta-ABAD interaction induces mitochondrial dysfunction: increased reactive oxygen species, altered membrane permeability, and caspase-3 activation.
  • Impaired Krebs cycle activity was noted as a consequence of mitochondrial dysfunction.
  • ABAD decoy peptide successfully blocked Abeta-induced mitochondrial dysfunction.

Conclusions:

  • Abeta-induced mitochondrial dysfunction, mediated by ABAD, is a significant factor in Alzheimer's disease pathogenesis.
  • Targeting the Abeta-ABAD interaction presents a promising therapeutic strategy for Alzheimer's disease.
  • Mitochondrial pathways represent a potential therapeutic target for combating AD.

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