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Topographical distribution of synaptic-associated proteins in the neuritic plaques of Alzheimer's disease hippocampus

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Abstract

Studies of the molecular composition of the abnormal neuritic processes of the plaques in Alzheimer's disease (AD) have shown that these structures are immunoreactive with antibodies against growth-related molecules, synaptic/axonal proteins, and cytoskeletal proteins. These studies suggest that a subpopulation of abnormal neurites in the plaque are sprouting axons that eventually degenerate. To test this hypothesis further we studied the regional distribution of plaques in the hippocampus using a panel of monoclonal antibodies against synaptic proteins. With these antibodies we found a greater proportion of immunoreactive plaques compared to previous studies where a monoclonal antibody against synaptophysin was used. The most sensitive antobodies to detect neuritic plaques were SP11 and anti-p65, and the largest number of positive plaques was found in the entorhinal cortex and CA1 region. These results further support the theory that synaptic and axonal damage are involved in plaque formation in AD.

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Authors and Affiliations

  1. Department of Neurosciences, University of California, San Diego, School of Medicine, 92093-0624, La Jolla, CA, USA

    Eliezer Masliah, William G. Honer, Margaret Mallory, Michelle Voigt, Pinky Kushner, Lawrence Hansen & Robert Terry

  2. Berlex Biosciences, 94804-0099, Richmond, CA, USA

    Eliezer Masliah, William G. Honer, Margaret Mallory, Michelle Voigt, Pinky Kushner, Lawrence Hansen & Robert Terry

  3. Department of Psychiatry, University of British Columbia, Vancouver, Canada

    Eliezer Masliah, William G. Honer, Margaret Mallory, Michelle Voigt, Pinky Kushner, Lawrence Hansen & Robert Terry

Authors
  1. Eliezer Masliah
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  2. William G. Honer
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  3. Margaret Mallory
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  4. Michelle Voigt
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  5. Pinky Kushner
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  6. Lawrence Hansen
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  7. Robert Terry
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Additional information

Supported by NIH grants AG08201, AG08205, AG05131, AG10689 (to EM, RDT and LAH) and by a grant from the Alzheimer's Association/George F. Berlinger Memorial Faculty Scholar Award (to EM). WGH was supported by the British Columbia Health Research Foundation

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Masliah, E., Honer, W.G., Mallory, M. et al. Topographical distribution of synaptic-associated proteins in the neuritic plaques of Alzheimer's disease hippocampus. Acta Neuropathol 87, 135–142 (1994). https://doi.org/10.1007/BF00296182

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