title: Plaque formation in brain transplants exposed to human beta-amyloid precursor protein 695.
abstract: Abnormal processing of beta-amyloid precursor protein (APP) and precipitation of amyloidogenic beta A4 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 beta A4 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.
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Germany.
authors.forename: T A
authors.initials: TA
authors.lastname: Bayer
authors.forename: A
authors.initials: A
authors.lastname: Fossgreen
authors.forename: C
authors.initials: C
authors.lastname: Czech
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: O D
authors.initials: OD
authors.lastname: Wiestler
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000009:adverse effects* / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D016380:Brain Tissue Transplantation / Q000473:pathology*; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000378:metabolism; D013238:Stereotaxic Techniques
chemical_list: D016564:Amyloid beta-Protein Precursor