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Microtubular reorganization and dendritic growth response in alzheimer's disease
Author(s) -
McKee Ann C.,
Kowall Neil W.,
Kosik Kenneth S.
Publication year - 1989
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410260511
Subject(s) - neurite , filopodia , colocalization , biology , growth cone , cytoskeleton , synaptophysin , microbiology and biotechnology , microtubule , neuroscience , neurofibrillary tangle , neurofilament , hippocampus , sprouting , pathology , axon , senile plaques , alzheimer's disease , immunohistochemistry , actin , cell , medicine , in vitro , immunology , disease , biochemistry , botany , genetics
Cytoskeletal disruption is a key pathological feature of Alzheimer's disease (AD). We used refined immunocytochemical techniques to define the range of abnormalities affecting the microtubule system in AD hippocampus. Minimal tau and tubulin immunoreactivity was granular and accumulated in otherwise normal neuronal perikarya. As tau‐reactive neurofibrillary tangles formed, granular tau and tubulin staining diminished, and ubiquitin reactivity developed. In regions of high neurofibrillary tangle density, microtubule‐associated protein 2 (MAP2) histochemical features of remaining nontangled neurons included apical dendritic degeneration with proliferation of basal dendrites. In addition to perisomatic dendritic proliferation, there was massive sprouting of tau‐immunoreactive distal dystrophic neurites. Sprouting proximal dendrites and dystrophic neurites often demonstrated growth‐cone‐like lamellipodia and filopodia. Degeneration of the perisomatic proliferating dendrites was characterized by the accumulation of fibrillar tau immunoreactivity. The colocalization of MAP2 and tau in growth structures recapitulated their codistribution in developing neurites. The data suggest that extensive plasticity and growth response occur in tandem with neuronal degeneration in AD, and that reorganization of the cytoskeletal microtubule system may underlie these proliferative changes.