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Mechanisms of synaptic pathology in Alzheimer’s disease

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Ageing and Dementia

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 53))

Summary

Neurodegenerative disorders are characterized by damage to selective neuronal populations that could be followed or preceded by synaptic injury. Therefore, specific mutations in and other alterations of synaptic proteins might lead to particular neurodegenerative diseases. The predominant hypothesis is that these mutations result in an increased production of amyloid β-protein 1–42 which acts as a neurotoxin. However, it could also be postulated that amyloid precursor protein might play an important role in synaptic function and neuronal maintenance, and that its abnormal activity may lead to neurodegeneration. Recent studies have shown that amyloid precursor protein has an important role in regulating glutamate levels at the synaptic site by modulating the activity of glutamate transporters. The objectives of this manuscript are to highlight recent data supporting the hypothesis that neurodegeneration in Alzheimer’s disease might be the combined result of abnormal protective activity of amyloid precursor protein and amyloid β-protein toxicity.

This work was supported by NIH/NIA Grants AG10689, AG05131 and by Grants from the Alzheimer’s Disease and Related Disorders Association, Inc. and the Ruth K. Broad Foundation and EBEWE Research Iniciative

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Authors and Affiliations

  1. Departments of Neurosciences and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA

    E. Masliah

  2. Departments of Neurosciences, University of California San Diego, La Jolla, 92093-0624, CA, USA

    E. Masliah

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  1. E. Masliah
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Editors and Affiliations

  1. Ludwig-Boltzmann-Institut für Klinische Neurobiologie, Wien, Österreich, Austria

    K. Jellinger (Prof. Dr.) (Prof. Dr.)

  2. Universitätsklinik für Neurologie, Graz, Österreich, Austria

    F. Fazekas (Prof. Dr.) (Prof. Dr.)

  3. Institut für Experimentelle Pharmakologie, Forschungsinitiative EBEWE, Graz, Österreich, Austria

    M. Windisch (Dr.) (Dr.)

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Masliah, E. (1998). Mechanisms of synaptic pathology in Alzheimer’s disease. In: Jellinger, K., Fazekas, F., Windisch, M. (eds) Ageing and Dementia. Journal of Neural Transmission. Supplementa, vol 53. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6467-9_13

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  • DOI: https://doi.org/10.1007/978-3-7091-6467-9_13

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