Plaque biogenesis in brain aging and Alzheimer’s disease. II. Progressive transformation and developmental sequence of dystrophic neurites |
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Authors: | J H Su Brian J Cummings Carl W Cotman |
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Institution: | (1) Institute for Brain Aging and Dementia, University of California Irvine, Irvine, CA 92717-4550, USA e-mail: jsu@teri.bio.uci.edu, Tel.: +1-714-824-6324, Fax: +1-714-824-2071, US |
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Abstract: | Plaque-associated dystrophic neurites are a common pathological feature in the brains of patients with Alzheimer’s disease
(AD). In the present study, we investigated the relative abundance and progressive transformation of the amyloid precursor
protein (APP), neurofilament (NF) and paired helical filament (PHF) tau-positive dystrophic neurites, within plaques in non-demented
controls versus plaque-associated dystrophic neurites in mild or severe AD using double and triple immunolabeling. We also
determined the argentophilia of the various sub-populations of dystrophic neurites. In aged non-demented brain, approximately
half of the APP-positive plaques contained NF-immunopositive dystrophic neurites; rarely were PHF/tau-positive dystrophic
neurites detectable. In contrast, in the AD brain, three-fourths of the APP-positive plaques contained NF-positive dystrophic
neurites and half contained PHF/tau neurites. We also observed focal patches of hyper-phosphorylated NF and/or PHF/tau within
APP-immunopositive dystrophic neurites, which appeared similar to retrograde degeneration, whereas we never observed focal
accumulations of APP within NF- or PHF/tau-positive fibers. We hypothesize that plaque-associated dystrophic neurites within
plaques develop in a particular sequence: APP-positive dystrophic neurites appear first and are non-argentophilic. This is
followed by the appearance of NF-positive dystrophic neurites, where a subset of NF-positive dystrophic neurites are lightly
argentophilic. Over time, PHF/tau-positive dystrophic neurites develop and are strongly argentophilic. These data suggest
that dystrophic neurites can develop retrogradely from focal plaque damage to induce somatic and dendritic degeneration and
potentially contribute to neurofibrillary tangle formation.
Received: 22 September 1997 / Revised, accepted: 15 April 1998 |
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Keywords: | Dystrophic neurites Senile plaques Progressive transformation Developmental sequence Alzheimer’ s disease |
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