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AD and T2D are characterized by deposition of cerebral amyloid\u2010\u03b2 (A\u03b2) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD\u2010related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. A\u03b2 and IAPP amyloid co\u2010deposition increased tau phosphorylation, and a reduction in pancreatic \u03b2\u2010cell mass was detected in islets. Increased brain deposition and tau phosphorylation and reduced insulin levels and signaling were accompanied by extensive synaptic loss and decreased neuronal counts. A\u03b2 immunization rescued the peripheral insulin resistance and hyperglycemia, suggesting a role for A\u03b2 in T2D pathogenesis for individuals predisposed to AD. These findings demonstrate that A\u03b2 and IAPP are key factors in the overlapping pathologies of AD and T2D.\u2014Wijesekara, N., Ahrens, R., Sabale, M., Wu, L., Ha, K., Verdile, G., Fraser, P. E. Amyloid\u2010\u03b2 and islet amyloid pathologies link Alzheimer\u2019s disease and type 2 diabetes in a transgenic model. FASEB J. 31, 5409\u20135418 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700431r","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T20:40:28Z","timestamp":1502743228000},"page":"5409-5418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Amyloid\u2010\u03b2 and islet amyloid pathologies link Alzheimer\u2019s disease and type 2 diabetes in a transgenic model"],"prefix":"10.1096","volume":"31","author":[{"given":"Nadeeja","family":"Wijesekara","sequence":"first","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases and University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Ahrens","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases and University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miheer","family":"Sabale","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Curtin Health and Innovation Research Institute Curtin University Bentley Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wu","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases and University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Ha","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases and University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Verdile","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Curtin Health and Innovation Research Institute Curtin University Bentley Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases and University of Toronto Toronto Ontario Canada"},{"name":"Department of Medical Biophysics University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.07.009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/105828"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2798269"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2008.10.004"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199908000-00003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-268482"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00500.2011"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404183"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0499"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000645107"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2014.890934"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100710200"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.14.7283"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.2.372"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12529"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.08.019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161192"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05194.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000067426"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.8.8147"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/35050110"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt162"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7703com"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-10-j0001.2002"},{"key":"e_1_2_8_27_1","volume-title":"Topics in the Prevention, Treatment and Complications of Type 2 Diabetes","author":"Son S. 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