ISSN:
1432-0533
Keywords:
Key words Plaque formation
;
β-Amyloid precursor
;
protein
;
Alzheimer’s disease
;
Transplantation
;
βA4 peptide
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Abnormal processing of β-amyloid precursor protein (APP) and precipitation of amyloidogenic βA4 peptide have been implicated in the pathogenesis of Alzheimer’s disease (AD). In an attempt to generate an in vivo model of APP-associated pathology, we have introduced recombinant retroviral vectors harboring normal and mutant cDNAs for human neuron-specific APP 695 into fetal rat brain transplants. A minor population of recombinant neural cells with expression of APP was identified immunohistochemically in the grafts. The expression was maintained during an observation period of 9 months. Neurons with strong immunoreactivity for human APP exhibited markedly swollen perikarya and showed signs of cell degeneration. At 6 months post-transplantation, recombinant grafts developed APP-positive neuropil deposits with morphological features of neuritic plaques, but without βA4 peptide immunoreactivity. No difference was observed between wild-type APP and the mutant APP construct derived from a family with autosomal dominant AD. These observations indicate that long-term neuronal overexpression of human APP has the potential to generate APP plaques in the rodent brain.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004010050500
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