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Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer’s disease
Journal article   Open access

Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer’s disease

Roger B Knowles, Claire Wyart, Sergey V Buldyrev, Luis Cruz, Brigita Urbanc, Michael E Hasselmo, H. Eugene Stanley and Bradley T Hyman
Proceedings of the National Academy of Sciences - PNAS, v 96(9), pp 5274-5279
27 Apr 1999
PMID: 10220456
url
https://doi.org/10.1073/pnas.96.9.5274View
Published, Version of Record (VoR) Open

Abstract

Biological Sciences
The brains of Alzheimer’s disease patients contain extracellular Aβ amyloid deposits (senile plaques). Although genetic evidence causally links Aβ deposition to the disease, the mechanism by which Aβ disrupts cortical function is unknown. Using triple immunofluorescent confocal microscopy and three-dimensional reconstructions, we found that neuronal processes that cross through an Aβ deposit are likely to have a radically changed morphology. We modeled the electrophysiological effect of this changed morphology and found a predicted delay of several milliseconds over an average plaque. We propose that this type of delay, played out among thousands of plaques throughout neocortical areas, disrupts the precise temporal firing patterns of action potentials, contributing directly to neural system failure and dementia.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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