{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:47:54Z","timestamp":1791092874799,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY028027"],"award-info":[{"award-number":["R01EY028027"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY029799"],"award-info":[{"award-number":["R01EY029799"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY032512"],"award-info":[{"award-number":["R01EY032512"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY031039"],"award-info":[{"award-number":["R01EY031039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG078892"],"award-info":[{"award-number":["R01AG078892"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG082108"],"award-info":[{"award-number":["R01AG082108"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA054992"],"award-info":[{"award-number":["R01DA054992"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008457","name":"University of Virginia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Inflammasome activation is implicated in Alzheimer's disease (AD). We previously demonstrated that nucleoside reverse transcriptase inhibitors (NRTIs), drugs approved to treat human immunodeficiency virus (HIV) and hepatitis B, also inhibit inflammasome activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We evaluated the association between NRTI exposure and subsequent development of AD in the United States Veterans Health Administration over a 24\u2010year period and in the MarketScan database over a 14\u2010year period using propensity score\u2010matched multivariate Cox hazards regression and Kaplan\u2013Meier analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We report that in humans, NRTI exposure was associated with a significantly lower incidence of AD in two of the largest health insurance databases in the United States. In contrast, exposure to non\u2010NRTIs, protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was not associated with reducing AD incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings support the concept that inflammasome inhibition could benefit AD and provide a rationale for prospective clinical testing of inflammasome inhibitors such as NRTIs in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Exposure to NRTIs, a class of anti\u2010retroviral drugs that also block inflammasome activation, was associated with a reduction in the risk of developing AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The reduction in risk was observed in two large, diverse health insurance databases after correcting for numerous comorbidities known to be associated with AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Other anti\u2010HIV therapies such as non\u2010NRTIs, protease inhibitors, and integrase strand transferase inhibitors were not associated with a reduction in the risk of developing AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our work provides a rationale for randomized clinical trials of inflammasome inhibitors in AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70180","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T07:00:13Z","timestamp":1746687613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Association of nucleoside reverse transcriptase inhibitor use with reduced risk of Alzheimer's disease risk"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-0097","authenticated-orcid":false,"given":"Joseph","family":"Magagnoli","sequence":"first","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Ambati","sequence":"additional","affiliation":[{"name":"Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy H.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire C.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya L.","family":"Ambati","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Scott","family":"Sutton","sequence":"additional","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley D.","family":"Gelfand","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Biomedical Engineering University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Pathology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayakrishna","family":"Ambati","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Pathology University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Microbiology Immunology, and Cancer Biology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.937486"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010022\u201000338\u20108"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.049"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.8522"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.08.039"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2923"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010016\u20100088\u20101"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.08.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1636"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010170634"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14945"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.721474"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11729"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.12.014"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101769\u2010z"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010018\u201001957\u2010y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.845185"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1261754"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010181259"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj3658"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018528\u2010z"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092101"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.10.4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022751118"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.4221"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17040408"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.03.17.23287375"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000537\u2010z"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.5.3"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44400-024-00001-z"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2010.526602"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1201"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282f08cdc"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00591\u201012"}],"container-title":["Alzheimer's &amp; 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