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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
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Amyloid-β peptides are generated in mitochondria-associated endoplasmic reticulum membranes

Bernadette Schreiner1, Louise Hedskog1, Birgitta Wiehager1

  • 1Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden.

Journal of Alzheimer'S Disease : JAD
|August 7, 2014
PubMed

Insights

Alzheimer's disease (AD) research reveals amyloid-beta (Aβ) peptides are produced at mitochondria-endoplasmic reticulum contact sites. This enhanced Aβ production may disrupt cellular functions, contributing to neurodegeneration in AD.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Extracellular amyloid-beta (Aβ) aggregates are a hallmark of Alzheimer's disease (AD).
  • Recent research indicates Aβ is generated intracellularly, with potential production sites including endosomes and the trans-Golgi network.

Purpose of the Study:

  • To determine the specific subcellular sites of Aβ production in mouse brain.
  • To investigate the role of mitochondria-endoplasmic reticulum (ER) contact sites in Aβ generation.

Main Methods:

  • Isolation of subcellular fractions from mouse brain.
  • Quantification of Aβ production within these fractions.

Main Results:

  • A significant amount of Aβ is produced at mitochondria-ER contact sites.
  • Specific sites include the outer mitochondrial membrane and mitochondria-associated ER membranes.
  • Enhanced Aβ production at these sites may impair ER, mitochondrial, and contact site functions.

Conclusions:

  • Mitochondria-ER contact sites are a key site for intracellular Aβ production.
  • Dysfunctional Aβ production at these sites may be a critical factor in Alzheimer's disease neurodegeneration.
Keywords:
Alzheimer's diseaseendoplasmic reticulum (ER)intracellular amyloid-β peptidesmitochondriamitochondria-ER contact sitesmitochondria-associated ER membranes (MAM)

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