{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T09:14:09Z","timestamp":1783502049553,"version":"3.55.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2018,1,9]]},"abstract":"<jats:p>\u00a0Alzheimer\u2019s disease (AD) is the most common tauopathy, characterized by progressive accumulation of amyloid-\u03b2 (A\u03b2) and hyperphosphorylated tau. While pathology associated with the 4-repeat (4R) tau isoform is more abundant in corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau isoforms accumulate in AD. Many studies have investigated interactions between A\u03b2 and 4R tau in double transgenic mice, but few, if any, have examined the effects of A\u03b2 with 3R tau. To examine this relationship, we crossed our APP751 mutant line with our recently characterized 3R tau mutant model to create a bigenic line (hAPP-3RTau) to model AD neuropathology. Mice were analyzed at 3 and 6 months of age for pathological and behavioral endpoints. While both the 3RTau and the hAPP-3RTau mice showed neuronal loss, increased tau aggregation, A\u03b2 plaques and exhibited more behavioral deficits compared to the non-tg control, the bigenic mice often displaying relatively worsening levels. We found that even in young animals we found that the presence of APP\/A\u03b2 increased the accumulation of 3R tau in the neocortex and hippocampus. This observation was accompanied by activation of GSK3 and neurodegeneration in the neocortex and CA1 region. These results suggest that in addition to 4R tau, APP\/A\u03b2 may also enhance accumulation of 3R tau, a process which may be directly relevant to pathogenic pathways in AD. Our results demonstrate that this bigenic model closely parallels the pathological course of AD and may serve as a valuable model for testing new pharmacological interventions.<\/jats:p>","DOI":"10.3233\/jad-170388","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T04:03:48Z","timestamp":1515557028000},"page":"1201-1219","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Increased Vulnerability of the Hippocampus in Transgenic Mice Overexpressing APP and Triple Repeat Tau"],"prefix":"10.1177","volume":"61","author":[{"given":"Andrew","family":"Arner","sequence":"first","affiliation":[{"name":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Rockenstein","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California 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