{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:27:53Z","timestamp":1792124873570,"version":"4.4.0"},"reference-count":131,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Instituto Carlos III de Madrid"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The identification of critical factors that can worsen the mechanisms contributing to the pathophysiology of Alzheimer disease is of paramount importance. Thyroid hormones (TH) fit this criterion. Epidemiological studies have identified an association between altered circulating TH levels and Alzheimer disease. The study of human and animal models indicates that TH can affect all the main cellular, molecular, and genetic mechanisms known as hallmarks of Alzheimer disease. This is true not only for the excessive production in the brain of protein aggregates leading to amyloid plaques and neurofibrillary tangles but also for the clearance of these molecules from the brain parenchyma via the blood-brain barrier and for the escalated process of neuroinflammation\u2014and even for the effects of carrying Alzheimer-associated genetic variants. Suboptimal TH levels result in a greater accumulation of protein aggregates in the brain. The direct TH regulation of critical genes involved in amyloid beta production and clearance is remarkable, affecting the expression of multiple genes, including APP (related to amyloid beta production), APOE, LRP1, TREM2, AQP4, and ABCB1 (related to amyloid beta clearance). TH also affects microglia by increasing their migration and function and directly regulating the immunosuppressor gene CD73, impacting the immune response of these cells. Studies aiming to understand the mechanisms that could explain how changes in TH levels can contribute to the brain alterations seen in patients with Alzheimer disease are ongoing. These studies have potential implications for the management of patients with Alzheimer disease and ultimately can contribute to devising new interventions for these conditions.<\/jats:p>","DOI":"10.1210\/endocr\/bqae124","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T04:34:43Z","timestamp":1726202083000},"source":"Crossref","is-referenced-by-count":9,"title":["Thyroid Hormone and Alzheimer Disease: Bridging Epidemiology to Mechanism"],"prefix":"10.1210","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0952-7506","authenticated-orcid":false,"given":"Sergio","family":"Escamilla","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias, CSIC-Universidad Miguel Hern\u00e1ndez , Alicante 03550 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , Alicante 03550 ,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria y Biom\u00e9dica de Alicante (ISABIAL) , Alicante 03010 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-5790","authenticated-orcid":false,"given":"Federico","family":"Salas-Lucia","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Chicago , Chicago, IL 60637 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"issue":"5","key":"2024100107254753300_bqae124-B1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S1474-4422(16)00062-4","article-title":"Defeating Alzheimer's disease and other dementias: a priority for European science and society","volume":"15","author":"Winblad","year":"2016","journal-title":"Lancet 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