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Distribution of neuronal growth-promoting factors and cytoskeletal proteins in altered neurites in Alzheimer's disease and non-demented elderly

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Abstract

In the present immunohistochemical study, we investigated the characteristics of altered neurites in the frontal cortex of 10 Alzheimer's disease (AD) brains and 15 age-matched non-demented control brains. In both AD and control cases, the altered neurites in coronas of the classical plaques (CP) were frequently immunostained by antibodies to growth-promoting factors, N and C termini of amyloid precursor protein (APP), GAP43, collagen IV, laminin and the integrin receptor VLA6. The altered neurites in CP coronas in AD but not in controls were also immunostained by antibodies against normally and abnormally phosphorylated tau. Immunolabeling for microtubule-associated protein 2 was not found in CP from either group. Extensive neuropil threads (NT) and many neurofibrillary tangles (NFT), immunostained with tau and Alz50 antibodies, were present in AD neocortex but not seen in control cases. NT and NFT could not be stained by antibodies to the N termini of APP, GAP43, collagen IV, laminin and VLA6. Our findings indicate that in AD cases altered neurites in CP are undergoing both an aberrant sprouting process and a degenerating process. These altered neurites are probably of axon origin. NT and NFT may represent destructive changes. The presence of amyloid plaques, but absence of tau-related cytoskeletal pathology, in non-demented cases suggests that β/A4 peptide is necessary but not sufficient to induce neurofibrillary pathology.

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Authors and Affiliations

  1. Department of Neuropathology, Free University Hospital, P.O. Box 7057, NL-1007 MB, Amsterdam, The Netherlands

    Shan-Shan Zhan & Wouter Kamphorst

  2. Department of Psychiatry, Medical Faculty, Free University, Amsterdam, The Netherlands

    Shan-Shan Zhan & Piet Eikelenboom

  3. Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California, USA

    William E. Van Nostrand

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  1. Shan-Shan Zhan
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  2. Wouter Kamphorst
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  3. William E. Van Nostrand
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  4. Piet Eikelenboom
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Zhan, SS., Kamphorst, W., Van Nostrand, W.E. et al. Distribution of neuronal growth-promoting factors and cytoskeletal proteins in altered neurites in Alzheimer's disease and non-demented elderly. Acta Neuropathol 89, 356–362 (1995). https://doi.org/10.1007/BF00309629

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