Cited by 738Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease

Caspersen, Casper, Wang, Ning, Yao, Jun, Sosunov, Alexander, Chen, Xi, Lustbader, Joyce W., Xu, Hong Wei, Stern, David +2 more·2005·The FASEB Journal

Abstract

Although amyloid-beta peptide (Abeta) is the neurotoxic species implicated in the pathogenesis of Alzheimer's disease (AD), mechanisms through which intracellular Abeta impairs cellular properties, resulting in neuronal dysfunction, remain to be clarified. Here we demonstrate that intracellular Abeta is present in mitochondria from brains of transgenic mice with targeted neuronal overexpression of mutant human amyloid precursor protein and AD patients. Abeta progressively accumulates in mitochondria and is associated with diminished enzymatic activity of respiratory chain complexes (III and IV) and a reduction in the rate of oxygen consumption. Importantly, mitochondria-associated Abeta, principally Abeta42, was detected as early as 4 months, before extensive extracellular Abeta deposits. Our studies delineate a new means through which Abeta potentially impairs neuronal energetics, contributing to cellular dysfunction in AD.

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Crossref · 10.1096/fj.05-3735fje

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76 of 76 references verified0 citation errors · 0 not checkable

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  • APP and Aβ, as well as the entire γ-secretase complex, physically associate with mitochondria and can effect changes in mitochondrial function.

    “accumulating data certainly do suggest APP and Aβ, as well as the entire γ-secretase complex, physically associate with mitochondria and can effect changes in mitochondrial function [58-67].”

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Authors
Caspersen, C., Wang, N., Yao, J., Sosunov, A., Chen, X., Lustbader, J. W., Xu, H. W., Stern, D., McKhann, G., & Du Yan, S.
Affiliations
  • Columbia University Irving Medical Center (US)
  • Fujian Medical University (CN)
  • University of Cincinnati (US)
  • Department of Surgery College of Physicians & Surgeons of Columbia University 630 West 168th Street New York NY 10032
Venue
The FASEB Journal
Publisher
Wiley
Published
2005-10-06
Volume
19
Issue
14
Pages
2040-2041
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W2103024032
Cited by
738
References
77
Citations by year
2026: 12 · 2025: 22 · 2024: 23 · 2023: 29 · 2022: 31 · 2021: 43 · 2020: 46 · 2019: 41 · 2018: 32 · 2017: 38 · 2016: 39 · 2015: 26 · 2014: 40 · 2013: 54 · 2012: 58
FWCI
13.84
Type
journal article
Language
en
Open access
closed
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Michael J. Fox Foundation for Parkinson's Research (P50 AG08702, AG16736, P01 AG17490, NS 042855)
  • Hørslev-Fonden
  • Sundhed og Sygdom, Det Frie Forskningsråd
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, Alzheimer's disease, respiratory chain complexes, cytochrome bc1 complex, cytochrome c oxidase, oxygen consumption, amyloid-beta 42, amyloid precursor protein, transgenic mice
MeSH terms
Alzheimer Disease, Animals, Brain, Cerebral Cortex, Cytosol, Energy Metabolism, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Models, Biological, Mutation, Neurons, Oxygen Consumption, Peptide Fragments, Peptide Hydrolases, Protein Synthesis Inhibitors, Time Factors, Immunoblotting, Amyloid beta-Peptides, Microscopy, Immunoelectron, Oxidative Stress, Microscopy, Confocal, Brefeldin A, Electron Transport Chain Complex Proteins, Mice, Plaque, Amyloid

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