{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:12:40Z","timestamp":1789240360993,"version":"build-2803163510"},"reference-count":41,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Late-onset Alzheimer\u2019s disease (LOAD) represents a growing health burden. Previous studies suggest that blood metabolite levels influence risk of LOAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We used a genetics-based study design which may overcome limitations of other epidemiological studies to assess the influence of metabolite levels on LOAD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We applied Mendelian randomization (MR) to evaluate bi-directional causal effects using summary statistics from the largest genome-wide association studies (GWAS) of 249 blood metabolites (\n                      <jats:italic>n<\/jats:italic>\n                      \u200a=\u200a115,082) and GWAS of LOAD (n\n                      <jats:sub>case<\/jats:sub>\n                      \u200a=\u200a21,982, n\n                      <jats:sub>control<\/jats:sub>\n                      \u200a=\u200a41,944).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>MR analysis of metabolites as exposures revealed a negative association of genetically-predicted glutamine levels with LOAD (Odds Ratio (OR)\u200a=\u200a0.83, 95% CI\u200a=\u200a0.73, 0.92) that was consistent in multiple sensitivity analyses. We also identified a positive association of genetically-predicted free cholesterol levels in small LDL (OR\u200a=\u200a1.79, 95% CI\u200a=\u200a1.36, 2.22) on LOAD. Using genetically-predicted LOAD as the exposure, we identified associations with phospholipids to total lipids ratio in large LDL (OR\u200a=\u200a0.96, 95% CI\u200a=\u200a0.94, 0.98), but not with glutamine, suggesting that the relationship between glutamine and LOAD is unidirectional.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings support previous evidence that higher circulating levels of glutamine may be a target for protection against LOAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-231063","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T12:02:09Z","timestamp":1710504129000},"page":"1069-1078","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Mendelian Randomization of Blood Metabolites Suggests Circulating Glutamine Protects Against Late-Onset Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"98","author":[{"given":"Ferris A.","family":"Ramadan","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayatri","family":"Arani","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayan","family":"Jafri","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L.","family":"Bland","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Renquist","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Raichlen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Anthropology, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene E.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Arizona, Tucson, AZ, USA"},{"name":"BIO5 Institute, University of 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