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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
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Identification and Characterization of Amyloid-β Accumulation in Synaptic Mitochondria

Shi Fang Yan1, Firoz Akhter2, Alexander A Sosunov3

  • 1Department of Pharmacology and Toxicology, Higuchi Bioscience Center, School of Pharmacy, University of Kansas, Lawrence, KS, USA. sfangyan@ku.edu.

Methods in Molecular Biology (Clifton, N.J.)
|June 11, 2018
PubMed

Insights

This study details a method to isolate synaptic mitochondria and measure amyloid beta-peptide (Aβ) levels, crucial for understanding Alzheimer's disease (AD) mitochondrial pathology and synaptic failure.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mitochondrial and synaptic dysfunction are early signs of Alzheimer's disease (AD).
  • Amyloid beta-peptide (Aβ) accumulation in synaptic mitochondria exacerbates synaptic injury and transmission disruption.
  • Understanding Aβ's role in synaptic mitochondria is key to Alzheimer's research.

Purpose of the Study:

  • To present a detailed methodology for isolating synaptic mitochondria from brain tissue.
  • To establish methods for determining Aβ levels within isolated synaptic mitochondria.
  • To enable ultrastructural localization of Aβ in synaptic mitochondria.

Main Methods:

  • Isolation of synaptic mitochondria from brain tissues.
  • Quantification of Aβ levels in isolated mitochondria.
  • Ultrastructural analysis for Aβ localization within mitochondria.

Main Results:

  • Successful isolation and characterization of synaptic mitochondria from AD mouse models.
  • Demonstration of Aβ accumulation within synaptic mitochondria.
  • Validation of the methodology for studying mitochondrial amyloid pathology.

Conclusions:

  • The presented methods are effective for analyzing Aβ in synaptic mitochondria.
  • This technique aids in understanding the mechanisms of synaptic dysfunction in Alzheimer's disease.
  • The methodology supports further research into mitochondrial amyloid pathology.
Keywords:
AβBrainELISAElectron microscopy (EM)ImmunoblottingImmunogold EMPercoll density gradient centrifugationSynaptic mitochondria

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