{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:41:15Z","timestamp":1793313675742,"version":"4.5.0"},"reference-count":265,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNRS"},{"name":"Universit\u00e9 Paris Cit\u00e9","id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The global prevalence of diabetes mellitus and Alzheimer\u2019s disease is increasing alarmingly with the aging of the population. Numerous epidemiological data suggest that there is a strong association between type 2 diabetes and an increased risk of dementia. These diseases are both degenerative and progressive and share common risk factors. The amyloid cascade plays a key role in the pathophysiology of Alzheimer\u2019s disease. The accumulation of amyloid beta peptides gradually leads to the hyperphosphorylation of tau proteins, which then form neurofibrillary tangles, resulting in neurodegeneration and cerebral atrophy. In Alzheimer\u2019s disease, apart from these processes, the alteration of glucose metabolism and insulin signaling in the brain seems to induce early neuronal loss and the impairment of synaptic plasticity, years before the clinical manifestation of the disease. The large amount of evidence on the existence of insulin resistance in the brain during Alzheimer\u2019s disease has led to the description of this disease as \u201ctype 3 diabetes\u201d. Available animal models have been valuable in the understanding of the relationships between type 2 diabetes and Alzheimer\u2019s disease, but to date, the mechanistical links are poorly understood. In this non-exhaustive review, we describe the main molecular mechanisms that may link these two diseases, with an emphasis on impaired insulin and IGF-1 signaling. We also focus on GSK3\u03b2 and DYRK1A, markers of Alzheimer\u2019s disease, which are also closely associated with pancreatic \u03b2-cell dysfunction and type 2 diabetes, and thus may represent common therapeutic targets for both diseases.<\/jats:p>","DOI":"10.3390\/ijms232315287","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:13:12Z","timestamp":1670206392000},"page":"15287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["Type 2 Diabetes Mellitus and Alzheimer\u2019s Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-087X","authenticated-orcid":false,"given":"Rim","family":"Hamz\u00e9","sequence":"first","affiliation":[{"name":"Team Biology and Pathology of the Endocrine Pancreas, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Delangre","sequence":"additional","affiliation":[{"name":"Team Biology and Pathology of the Endocrine Pancreas, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-5810","authenticated-orcid":false,"given":"Stefania","family":"Tolu","sequence":"additional","affiliation":[{"name":"Team Biology and Pathology of the Endocrine Pancreas, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Moreau","sequence":"additional","affiliation":[{"name":"Team Degenerative Process, Stress and Aging, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Janel","sequence":"additional","affiliation":[{"name":"Team Degenerative Process, Stress and Aging, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Bailb\u00e9","sequence":"additional","affiliation":[{"name":"Team Biology and Pathology of the Endocrine Pancreas, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-1525","authenticated-orcid":false,"given":"Jamileh","family":"Movassat","sequence":"additional","affiliation":[{"name":"Team Biology and Pathology of the Endocrine Pancreas, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, CNRS, Universit\u00e9 Paris Cit\u00e9, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.neubiorev.2016.03.005","article-title":"Diabetes and Alzheimer\u2019s Disease Crosstalk","volume":"64","author":"Shi","year":"2016","journal-title":"Neurosci. 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