Selective deposition of amyloid-beta protein in the entorhinal-dentate projection of a transgenic mouse model of Alzheimer's disease.
Early and selective deposition of amyloid beta protein(Abeta) is thought to be a pathological feature central to Alzheimer's disease (AD). It has been a great challenge to identify the mechanism(s) responsible for the selectivity of Abeta deposition and the deposition into a temporal sequence of the pathogenesis in this disorder. We now report that the transgenic mouse (PDAPP), which overexpresses the human amyloid precursor protein containing the familial AD mutation (APP717V-F), develops brain region-specific Abeta deposits along with some pathologies associated with AD. By using monoclonal antibodies that recognize multiple sites on the human Abeta peptide, we show that Abeta deposits are localized primarily to the entorhinal cortex and hippocampal/dentate gyrus regions. Abeta deposition exhibited consistent laminar distribution throughout the hippocampal formation that was confined mostly to a dense terminal field in the outer portion of the stratum moleculare of the dentate gyrus and the stratum lacunosum of the hippocampus proper of 13-month-old heterozygous PDAPP mice. Abeta deposits were also observed in the supragranular zone of the dentate gyrus. Similarly, laminar distribution of Abeta deposits were evident in the entorhinal cortex, most notably in the molecular layer and in laminar layer II-III. The defined laminar pattern of the Abeta deposition, which resembles that of AD, suggests that intrinsic factors in the perforant path, the major projection from the entorhinal cortex to the hippocampal formation, and their respective local paths contribute, at least in part, to the extracellular Abeta deposition in the transgenic mouse model of AD.
Division of Neuroscience Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
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D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal