Mechanisms of cell death in Alzheimer disease — immunopathology (original) (raw)

Summary

Lesions in such chronic neurodegenerative disorders as Alzheimer disease, Parkinson disease, the parkinsonism dementia complex of Guam and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is particularly true of Alzheimer disease where inflammatory reactions are thought to be important contributors to the neuronal loss. They include complement proteins, complement inhibitors, acute phase reactants, inflammatory cytokines, proteases and protease inhibitors. Studies of cultured human astrocytes and microglia, obtained from postmortem brain, have established that nearly all of these proteins are produced by one or another of these cell types. Human neurons also produce many inflammatory proteins and their inhibitors, creating complex interactions. Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen free radicals and excess glutamate. Twenty epidemiological studies that have been published to data indicate that populations taking antiinflammatory drugs have a significantly reduced prevalence of Alzheimer disease or a slower mental decline. One small clinical trial with indomethacin showed arrest of the disease over a 6 month period. Thera peutic intervention in key inflammatory processes holds great promise for the amelioration of Alzheimer disease and possibly other neurodegenerative disorders.

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Authors and Affiliations

1. Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B.C., V6T 1Z3, Canada
   Dr. P. L. McGeer & E. G. McGeer

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1. Dr. P. L. McGeer
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2. E. G. McGeer
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Editors and Affiliations

1. Klinik und Poliklinik für Psychiatrie, Universität Leipzig, Bundesrepublik Deutschland
   H.-J. Gertz
2. Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Bundesrepublik Deutschland
   Th. Arendt

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© 1998 Springer-Verlag/Wien

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McGeer, P.L., McGeer, E.G. (1998). Mechanisms of cell death in Alzheimer disease — immunopathology. In: Gertz, HJ., Arendt, T. (eds) Alzheimer’s Disease — From Basic Research to Clinical Applications. Journal of Neural Transmission. Supplementa, vol 54. Springer, Vienna. https://doi.org/10.1007/978-3-7091-7508-8\_15

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• DOI: https://doi.org/10.1007/978-3-7091-7508-8\_15
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