{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:45:41Z","timestamp":1761237941466},"reference-count":63,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T00:00:00Z","timestamp":1361318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2013,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse\/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid\u2010\u03b2 precursor protein (A\u03b2PP) and presenilin\u20101 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. A\u03b2PP\/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4\u20139 months of age. We crossed A\u03b2PP\/PS1 animals with mice of a mixed genetic background (C57BL\/6 \u00d7 129\/SvJ) and investigated the development of AD\u2010like features in the resulting outcrossed mice. The onset of memory\u2010based behavioral impairment is delayed considerably in outcrossed A\u03b2PP\/PS1 mice relative to inbred mice on a C57BL\/6 background. While inbred A\u03b2PP\/PS1 mice develop deficits in radial\u2010arm water maze performance and novel object recognition as early as 8 months, outcrossed A\u03b2PP\/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred A\u03b2PP\/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed A\u03b2PP\/PS1 mice of the same age. Surprisingly, inbred A\u03b2PP\/PS1 mice at 8 months have low plaque burden, suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of A\u03b2PP processing revealed that elevated levels of soluble A\u03b2 correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and A\u03b2PP processing are sensitive to genetic differences between mouse strains. J. Comp. Neurol., 521:1395\u20131408, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23239","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T07:42:05Z","timestamp":1349854925000},"page":"1395-1408","source":"Crossref","is-referenced-by-count":6,"title":["Delayed amyloid plaque deposition and behavioral deficits in outcrossed A\u03b2PP\/PS1 mice"],"prefix":"10.1002","volume":"521","author":[{"given":"Brian A.","family":"Couch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan E.","family":"Kerrisk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam C.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haakon B.","family":"Nygaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen 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