Cited by 172Alzheimer's disease research and treatmentsCell death mechanisms and regulationNeuroinflammation and Neurodegeneration Mechanisms

Rapid cell death is preceded by amyloid plaque-mediated oxidative stress

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Xie, Hong, Hou, Steven, Jiang, Jun, Sekutowicz, Maria, Kelly, Jonathan, Bacskai, Brian J.·2013·Proceedings of the National Academy of Sciences

Abstract

Neuronal loss is the ultimate outcome in a variety of neurodegenerative diseases and central nerve system disorders. Understanding the sequelae of events that leads to cell death would provide insight into neuroprotective approaches. We imaged neurons in the living brain of a mouse model of Alzheimer's disease that overexpresses mutant human amyloid precursor protein and presenilin 1 and followed the death of individual neurons in real time. This mouse model exhibited limited neurodegeneration and atrophy, but we were able to identify a small fraction of vulnerable cells that would not have been detectable by using standard approaches. By exploiting a genetically encoded reporter of oxidative stress, we identified susceptible neurons by their increased redox potential. The oxidative stress was most dramatic in neurites near plaques, propagated to cell bodies, and preceded activation of caspases that led to cell death within 24 h. Thus, local oxidative stress surrounding plaques contributes to long-range toxicity and selective neuronal death in Alzheimer's disease.

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  • Local oxidative stress surrounding plaques has been proposed as a potential mechanism contributing to selective neuronal death.

    “and local oxidative stress surrounding plaques has been proposed as a potential mechanism contributing to selective neuronal death [37].”

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  1. [30]Spires TL, et al. Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci. 2005;25(31):7278–7287. doi: 10.1523/JNEUROSCI.1879-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page

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Authors
Xie, H., Hou, S., Jiang, J., Sekutowicz, M., Kelly, J., & Bacskai, B. J.
Affiliations
  • Massachusetts General Hospital (US)
  • Tsinghua University (CN)
Venue
Proceedings of the National Academy of Sciences
Published
2013-04-22
Volume
110
Issue
19
Pages
7904-7909
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2086831255
Cited by
172
References
29
Citations by year
2026: 8 · 2025: 13 · 2024: 15 · 2023: 11 · 2022: 12 · 2021: 14 · 2020: 16 · 2019: 17 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 13 · 2014: 14 · 2013: 8
FWCI
10.65
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG024688, R01AG024688)
  • National Institute of Biomedical Imaging and Bioengineering (EB 000768, R01EB000768)
  • National Center for Research Resources (S10RR025645)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid plaques, oxidative stress, neuronal cell death, presenilin 1, amyloid precursor protein, caspase activation, neurodegeneration, neuroprotection
MeSH terms
Alzheimer Disease, Animals, Atrophy, Gene Expression Regulation, Image Processing, Computer-Assisted, Mice, Transgenic, Neurons, Oxidation-Reduction, Time Factors, Cell Death, Oxidative Stress, Caspases, Green Fluorescent Proteins, Mice, Plaque, Amyloid

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