{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:56:59Z","timestamp":1772632619435,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>TAS2R38 is a taste receptor gene located on human chromosome 7 that influences sensitivity to bitter tastes and has been implicated in innate immunity, glucose level, and human longevity. However, its potential association with Alzheimer\u2019s Disease (AD) has not been explored. Identifying such a genetic connection could support developing new drugs or repurposing existing ones for AD treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this work, we examined the relationship between allele counts of TAS2R38 taster variants and AD risk using linear mixed-effects models, utilizing genetic, clinical, and biomarker data from the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI). We investigated the potential molecular mechanisms of the association by identifying expression quantitative trait loci (eQTLs) using RNA-seq data from postmortem tissues across brain regions from the Religious Orders Study\/Memory and Aging Project (ROSMAP). We evaluated whether FDA-approved drugs targeting the identified e-gene could reduce dementia risk using 1:1 propensity score-matched groups from longitudinal data in the National Alzheimer\u2019s Coordinating Center (NACC) study, by comparing clinical dementia progression trends between the drug-taking and non-taking groups with linear mixed-effects models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results show that TAS2R38 supertasters were connected to a reduced AD risk with advancing age due to its association with various AD biomarkers (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). eQTL analysis linked the nontaster allele to increased expression of the gene MGAM in AD-affected brain regions (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Furthermore, elevated MGAM expression correlated with more severe Tau burden (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05) and implicated in mitochondrial dysfunction in AD subjects. Notably, MGAM is a known drug target for diabetes mellitus. In NACC data, individuals taking MGAM-inhibiting drugs (acarbose and miglitol) showed slower clinical dementia rating progression (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) in comparison with the non-taking group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study is the first to report a genetic association between TAS2R38 and AD biomarkers. Our findings, validated in multiple cohorts\/matching groups, suggest MGAM as a novel AD drug target with existing FDA-approved inhibitors and demonstrate the potential of TAS2R38 haplotypes to inform precision drug repurposing strategies for AD, which warrants further in-depth preclinical and clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1768436","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:02:47Z","timestamp":1772607767000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TAS2R38 taster variants-linked MGAM expression in Alzheimer\u2019s disease: a novel target for precision drug repurposing"],"prefix":"10.3389","volume":"18","author":[{"given":"Claire W.","family":"Su","sequence":"first","affiliation":[{"name":"School of Computing and Augmented Intelligence, Arizona State University","place":["Tempe, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kewei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University","place":["Tempe, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Computing and Augmented Intelligence, Arizona State University","place":["Tempe, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric M.","family":"Reiman","sequence":"additional","affiliation":[{"name":"Banner Alzheimer\u2019s Institute","place":["Phoenix, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"ASU-Banner Neurodegenerative Disease Research Center, Arizona State University","place":["Tempe, AZ, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1056\/NEJMsr1809937","article-title":"The \u201cAll of Us\u201d research program.","volume":"381","author":"Denny","year":"2019","journal-title":"N. 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