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Research","award":["TED2021-130174B-C33"],"award-info":[{"award-number":["TED2021-130174B-C33"]}]},{"name":"fellowships from the Council of Scientific and Industrial Research","award":["PID2022-138585OB-C33"],"award-info":[{"award-number":["PID2022-138585OB-C33"]}]},{"name":"fellowships from the Council of Scientific and Industrial Research","award":["09\/015(0553)\/2020-EMR-I"],"award-info":[{"award-number":["09\/015(0553)\/2020-EMR-I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A hallmark of type 2 diabetes mellitus (T2DM) is the presence of abundant amyloid deposits composed of amyloid polypeptide (amylin) within the pancreatic islets of Langerhans. Given its high prevalence among diabetic individuals, human amylin fibrillization has long been considered a key pathogenic factor in T2DM. Co-secreted with insulin, amylin can misfold and aggregate, inducing \u03b2-cell toxicity, impairing insulin secretion, and accelerating disease progression. Emerging evidence also indicates that amylin accumulates in the brains of patients with Alzheimer\u2019s disease, where it may interact with amyloid-\u03b2 (A\u03b2) to promote neurodegeneration. Although the underlying mechanisms remain under investigation, amylin aggregates have been shown to disrupt mitochondrial function, trigger endoplasmic reticulum stress, and activate the NLRP3 inflammasome. Additionally, T2DM-associated cerebrovascular alterations may compound cognitive decline. This review, based on a comprehensive literature search across major biomedical databases up to January 2025, synthesizes current evidence on amylin as a molecular link between metabolic and neurodegenerative disorders. We highlight pancreatic \u03b2-cell amylin aggregation as a potential early marker of dementia risk in T2DM and examine its relationship with proteostasis-associated proteins. Finally, we discuss emerging diagnostic and therapeutic strategies targeting amylin pathology, offering new perspectives on preventing or delaying neurodegeneration in individuals with T2DM.<\/jats:p>","DOI":"10.3390\/ijms26115021","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:16:03Z","timestamp":1747980963000},"page":"5021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bridging Pancreatic Amyloidosis and Neurodegeneration: The Emerging Role of Amylin in Diabetic Dementia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-5029","authenticated-orcid":false,"given":"Gourav","family":"Shome","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Bose Institute, Kolkata 700054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-7661","authenticated-orcid":false,"given":"Ritwick","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Manipal Group of Hospitals Kolkata, Kolkata 700099, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shramana","family":"Deb","sequence":"additional","affiliation":[{"name":"Department of Neurology, Manipal Group of Hospitals Kolkata, Kolkata 700099, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanta","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Manipal Group of Hospitals Kolkata, Kolkata 700099, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atin Kumar","family":"Mandal","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bose Institute, Kolkata 700054, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-4809","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Benito-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Group of Neurodegenerative Diseases, Hospital Universitario 12 de Octubre Research Institute (imas12), 28041 Madrid, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"},{"name":"Department of Medicine, Faculty of Medicine, Complutense University, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrd3050","article-title":"Protein aggregation diseases: Pathogenicity and therapeutic perspectives","volume":"9","author":"Aguzzi","year":"2010","journal-title":"Nat. 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