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Nevertheless, rather than being merely a form of LOAD that occurs at a prematurely defined younger age, EOAD differs from LOAD in multiple ways. Given these disparities, understanding the potential treatment options for EOAD becomes crucial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:\u2002<\/jats:title>\n                    <jats:p>We aim to assess anti-diabetic drugs\u2019 potential utility in treating EOAD and LOAD from a novel perspective via drug-targeted Mendelian randomization (MR) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:\u2002<\/jats:title>\n                    <jats:p>Through Summary-data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) analysis, we assessed the associations between anti-diabetic drug targets (including DPP-4 inhibitor, Thiazolidinedione, GLP1R agonist, Sulfonylureas, SLC5A2 inhibitor, and Insulin\/Insulin analog) and AD outcomes (EOAD and LOAD). We utilized two types of genetic instruments to represent the exposure to anti-diabetic drugs: eQTLs of genes encoding drug target proteins and genetic variants within or near genes encoding these target proteins associated with HbA1c from genome-wide association studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:\u2002<\/jats:title>\n                    <jats:p>\n                      SMR analysis showed that enhanced PPARG gene expression in the blood was a protective factor for EOAD (OR = 0.733, 95%CI\u2009=\u20090.548\u20130.979,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.035). Additionally, an IVW-MR association was found between HbA1c mediated by PPARG and EOAD (OR = 0.295, 95%CI\u2009=\u20090.092\u20130.949,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.041).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:\u2002<\/jats:title>\n                    <jats:p>This study suggests that Thiazolidinedione therapy could help suppress the development of EOAD, supporting further exploration of PPARG-targeted anti-diabetic drug development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25424823251359579","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:55:13Z","timestamp":1753095313000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Association between genetically proxied PPARG activation and early onset Alzheimer's disease: A drug target Mendelian randomization study"],"prefix":"10.1177","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3121-2984","authenticated-orcid":false,"given":"Lingyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Experimental Animal Center of Shanxi Medical University, Shanxi Key Laboratory of Human Disease and Animal Models, Taiyuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanxi Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanxi Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Experimental Animal Center of Shanxi Medical University, Shanxi Key Laboratory of Human Disease and Animal Models, Taiyuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0891988710383571"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-132273"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-143207"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1471301212474149"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/1533317512459798"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/1533317513494443"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2015.11.011"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70119-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000140292.04932.87"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720507780362137"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0124"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31822f0435"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00314304"},{"key":"e_1_3_3_15_2","first-page":"180","article-title":"Blood supply and metabolism of the brain in substantial traumatic brain damage","volume":"42","author":"Hoyer S","year":"1971","unstructured":"Hoyer S, Oesterreich K. 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