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The etiologies of Parkinson\u2019s and Alzheimer\u2019s disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. As we have previously demonstrated the presence of \u03b1-synuclein deposits in the pancreas of patients with synucleinopathies, as well as tau and A\u03b2 deposits in the pancreatic tissue of Alzheimer\u2019s disease patients, we studied the immunoreactivity of amylin, tau and \u03b1-synuclein in the pancreas of 138 subjects with neurodegenerative diseases or type two diabetes and assessed whether the pancreatic \u03b2-cells of these subjects present cooccurrence of misfolded proteins. Furthermore, we also assessed the pancreatic expression of prion protein (PrP) in these subjects and its interaction, both in the pancreas and brain, with \u03b1-synuclein, tau, A\u03b2 and amylin. Our study shows, for the first time, that along with amylin, pancreatic \u03b1-synuclein, A\u03b2, PrP and tau may contribute together to the complex pathophysiology of type two diabetes and in the appearance of insulin resistance in Alzheimer\u2019s and Parkinson\u2019s disease. Furthermore, we show that the same mixed pathologies that are observed in the brains of patients with neurodegenerative diseases are also present outside the nervous system. Finally, we provide the first histological evidence of an interaction between PrP and A\u03b2, \u03b1-synuclein, amylin or tau in the pancreas and <jats:italic>locus coeruleus<\/jats:italic>. These findings will shed more light on the common pathological pathways shared by neurodegenerative diseases and type two diabetes, benefiting the exploration of common therapeutic strategies to prevent or treat these devastating amyloid diseases.<\/jats:p>","DOI":"10.1186\/s40478-021-01171-0","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T08:03:39Z","timestamp":1617869019000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Mixed pathologies in pancreatic \u03b2 cells from subjects with neurodegenerative diseases and their interaction with prion protein"],"prefix":"10.1186","volume":"9","author":[{"given":"Ivan","family":"Martinez-Valbuena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Valenti-Azcarate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Amat-Villegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Marcilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Marti-Andres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Cristina","family":"Caballero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Riverol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Teresa","family":"Tu\u00f1on","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-1794","authenticated-orcid":false,"given":"Mar\u00eda-Rosario","family":"Luquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"1171_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s00401-009-0523-2","volume":"117","author":"I Alafuzoff","year":"2009","unstructured":"Alafuzoff I, Ince PG, Arzberger T, Al-Sarraj S, Bell J, Bodi I, Bogdanovic N, Bugiani O, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Ironside JW, Kavantzas N, King A, Korkolopoulou P, Kov\u00e1cs GG, Meyronet D, Monoranu C, Parchi P, Parkkinen L, Patsouris E, Roggendorf W, Rozemuller A, Stadelmann-Nessler C, Streichenberger N, Thal DR, Kretzschmar H (2009) Staging\/typing of Lewy body related \u03b1-synuclein pathology: a study of the BrainNet Europe Consortium. 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