{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:54:52Z","timestamp":1790135692283,"version":"4.0.1"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"48","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,11,30]]},"abstract":"\n According to the prevailing \u201camyloid cascade hypothesis,\u201d genetic dementias such as Alzheimer\u2019s disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral\/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mechanisms cause Danish dementia. We studied an animal knock-in model of FDD (FDD\n KI\/+<\/jats:sub>\n ) genetically congruous with human cases. FDD\n KI\/+<\/jats:sub>\n mice present reduced Bri2 levels, impaired synaptic plasticity and severe hippocampal memory deficits. These animals show no cerebral lesions that are reputed characteristics of human dementia, such as tangles or amyloid plaques.\n Bri2<\/jats:italic>\n +\/\u2212<\/jats:sup>\n mice exhibit synaptic and memory deficits similar to FDD\n KI\/+<\/jats:sub>\n mice, and memory loss of FDD\n KI\/+<\/jats:sub>\n mice is prevented by expression of WT BRI2, indicating that Danish dementia is caused by loss of BRI2 function. Together, the data suggest that clinical dementia in Danish patients occurs via a loss of function mechanism and not as a result of amyloidosis and tauopathy.\n <\/jats:p>","DOI":"10.1073\/pnas.1011689107","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T00:41:46Z","timestamp":1290472906000},"page":"20822-20827","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits"],"prefix":"10.1073","volume":"107","author":[{"given":"Robert","family":"Tamayev","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"F\u00e0","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavio","family":"Arancio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"D\u2019Adamio","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,11,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.080076097"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0730fje"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00164.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001056107"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608332104"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08177"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00182-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007900"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.43701"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.04.004"},{"key":"e_1_3_3_11_2","first-page":"274","volume":"106","author":"Matsuda S","year":"1992","unstructured":"S Matsuda, Y Matsuda, EL Snapp, L D\u2019Adamio Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles. (Neurobiol Aging). Behav Neurosci 106, 274\u2013285 (1992).","journal-title":"Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles. (Neurobiol Aging). 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