{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:58:35Z","timestamp":1793663915790,"version":"4.5.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2500502"],"award-info":[{"award-number":["2021YFC2500502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Phenylalanine (Phe) and its metabolite tyrosine (Tyr) have been shown to play an important role in the mechanisms and development of cardiovascular and cerebrovascular disease, and its ratio (Phe\/Tyr) has been suggested to be an important indicator of inflammation. It was uncertain whether Phe\/Tyr is associated with higher risk of MMD. Therefore, we conducted this study to evaluate the relationship between Phe\/Tyr and the risk of MMD and its subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 360 adult MMD patients and 89 age-matched healthy controls (HCs) were consecutively recruited for this prospective study. We measured peripheral blood serum Phe and Tyr levels in all participants to analyze the association between Phe\/Tyr and the risk of MMD and its subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum Phe\/Tyr was significantly higher in MMD patients and their subtypes than in HCs (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.01). After adjusting for traditional risk factors, Phe\/Tyr was positively associated with the risk of MMD (OR: 14.035, 95%CI: 2.784\u201370.748, <jats:italic>p<\/jats:italic>\u202f=\u202f0.001). When Phe\/Tyr was assessed in quartile subgroups, the third quartile (Q3) and fourth quartile (Q4) subgroups of Phe\/Tyr had a significantly increased risk of MMD compared to the first quartile (Q3, OR: 2.019, 95%CI: 1.066\u20133.824, <jats:italic>p<\/jats:italic>\u202f=\u202f0.031; Q4, OR: 2.887, 95%CI: 1.446\u20135.765, <jats:italic>p<\/jats:italic>\u202f=\u202f0.003). The risk of MMD subtypes also increased with elevated Phe\/Tyr level. Meanwhile, the addition of Phe\/Tyr to conventional risk factors could significantly improve the risk prediction for MMD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study, the risk of MMD increased with elevated Phe\/Tyr, suggesting that peripheral blood serum Phe\/Tyr may be a valuable predictive biomarker of adult MMD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1554697","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T04:11:36Z","timestamp":1743653496000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between peripheral blood serum phenylalanine to tyrosine ratio and the risk of moyamoya disease: a case-control study"],"prefix":"10.3389","volume":"16","author":[{"given":"Shixiong","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengnan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peicong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/S1474-4422(08)70240-0","article-title":"Moyamoya 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