{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:04:49Z","timestamp":1787025889259,"version":"build-2736575974"},"reference-count":70,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,9,27]]},"abstract":"<jats:p>Background: The relationship between serum uric acid (UA) and Alzheimer\u2019s disease (AD) risk still remained ambiguous despite extensive attempts. Objective: Via the two-sample Mendelian randomization (MR) design, we aimed to examine the bidirectional causal relationships of serum UA, gout, and the risk of AD. Methods: Genetic variants of UA, gout, and AD were extracted from published genome-wide association summary statistics. The inverse-variance weighted (IVW, the primary method), and several sensitivity methods (MR-Egger, weighted median, and weighted mode) were used to calculate the effect estimates. Egger regression, MR-PRESSO and leave-one-SNP-out analysis were performed to identify potential violations. Results: Genetic proxies for serum UA concentration [odds ratio (ORIVW)\u200a=\u200a1.09, 95% confidence interval (CI)\u200a=\u200a1.01\u20131.19, p\u200a=\u200a0.031] were related with an increased risk of AD using 25 single nucleotide polymorphisms (SNPs). This causal effect was confirmed by sensitivity analyses including MR-Egger (1.22, 1.06\u20131.42, p\u200a=\u200a0.014), weighted median (1.18, 1.05\u20131.33, p\u200a=\u200a0.006), and weighted mode (1.20, 1.07\u20131.35, p\u200a=\u200a0.005) methods. No evidence of notable directional pleiotropy and heterogeneity were identified (p\u200a&gt;\u200a0.05). Three SNPs (rs2078267, rs2231142, and rs11722228) significantly drove the observed causal effects. Supportive causal effect of genetically determined gout on AD risk was demonstrated using two SNPs (ORIVW\u200a=\u200a1.05, 95% CI\u200a=\u200a1.00\u20131.11, p\u200a=\u200a0.057). No reverse causal effects of AD on serum UA levels and gout risk were found. Conclusion: The findings revealed a causal relationship between elevated serum UA level and AD risk. However, further research is still warranted to investigate whether serum UA could be a reliable biomarker and therapeutic target for AD.<\/jats:p>","DOI":"10.3233\/jad-220649","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T10:59:45Z","timestamp":1660301985000},"page":"1063-1073","source":"Crossref","is-referenced-by-count":14,"title":["The Association of Serum Uric Acid Level, Gout, and Alzheimer\u2019s Disease: A Bidirectional Mendelian Randomization Study"],"prefix":"10.1177","volume":"89","author":[{"given":"Ya-Nan","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Hu","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Tai","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220649_ref1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/539179a","article-title":"Neurodegenerative diseases","volume":"539","author":"Heemels","year":"2016","journal-title":"Nature"},{"key":"10.3233\/JAD-220649_ref2","doi-asserted-by":"crossref","unstructured":"(2022) 2022 Alzheimer\u2019s disease facts and figures. 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