{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:33:53Z","timestamp":1793446433670,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,11,25]]},"abstract":"<jats:p>\n                    Mutations in the amyloid precursor protein (APP) gene cause early-onset familial Alzheimer disease (AD) by affecting the formation of the amyloid \u03b2 (A\u03b2) peptide, the major constituent of AD plaques. We expressed human APP\n                    <jats:sub>751<\/jats:sub>\n                    containing these mutations in the brains of transgenic mice. Two transgenic mouse lines develop pathological features reminiscent of AD. The degree of pathology depends on expression levels and specific mutations. A 2-fold overexpression of human APP with the Swedish double mutation at positions 670\/671 combined with the V717I mutation causes A\u03b2 deposition in neocortex and hippocampus of 18-month-old transgenic mice. The deposits are mostly of the diffuse type; however, some congophilic plaques can be detected. In mice with 7-fold overexpression of human APP harboring the Swedish mutation alone, typical plaques appear at 6 months, which increase with age and are Congo Red-positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. The immunoreactivity is exclusively found in congophilic senile plaques of both lines. In the higher expressing line, elevated tau phosphorylation can be demonstrated biochemically in 6-month-old animals and increases with age. These mice resemble major features of AD pathology and suggest a central role of A\u03b2 in the pathogenesis of the disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.24.13287","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"13287-13292","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1279,"title":["Two amyloid precursor protein transgenic mouse models with Alzheimer\u2009disease-like\u2009pathology"],"prefix":"10.1073","volume":"94","author":[{"given":"Christine","family":"Sturchler-Pierrat","sequence":"first","affiliation":[{"name":"Novartis Pharma, Inc., S-386.809, CH-4002 Basel, Switzerland; and Institute for Pathology, University of Basel, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Abramowski","sequence":"additional","affiliation":[{"name":"Novartis Pharma, 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