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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

Amyloid-Beta interaction with mitochondria

Lucia Pagani1, Anne Eckert

  • 1Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Wilhelm Klein-Straße 27, 4012 Basel, Switzerland.

International Journal of Alzheimer'S Disease
|April 5, 2011
PubMed

Insights

Alzheimer's disease involves amyloid-beta (Aβ) damaging neurons. This study shows Aβ directly harms mitochondria, impacting energy production and increasing oxidative stress, supporting a revised Alzheimer cascade mitochondrial hypothesis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mitochondrial dysfunction is central to Alzheimer's disease (AD) neurotoxicity.
  • Amyloid-beta (Aβ) and its precursor (AβPP) are increasingly studied within cells, including mitochondria.

Purpose of the Study:

  • To explore the intracellular localization of Aβ and AβPP.
  • To investigate how Aβ accesses mitochondria.
  • To summarize evidence linking Aβ to mitochondrial dysfunction in AD.

Main Methods:

  • Review of current literature on Aβ/AβPP intracellular localization.
  • Analysis of evidence from postmortem AD brains, cell models, and animal models.
  • Focus on Aβ interactions with various mitochondrial compartments and proteins.

Main Results:

  • Aβ can access and accumulate within mitochondria.
  • Aβ disrupts mitochondrial function via impaired oxidative phosphorylation and increased reactive oxygen species (ROS).
  • Aβ alters mitochondrial dynamics and interacts with key mitochondrial proteins.

Conclusions:

  • Aβ directly induces mitochondrial dysfunction, contributing to neuronal toxicity in AD.
  • Aβ interacts with multiple mitochondrial targets, from the outer membrane to the matrix.
  • A modified Alzheimer cascade mitochondrial hypothesis is proposed based on these findings.

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