Sex-specific associations of kynurenic acid with neopterin in Alzheimer’s disease

IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Alzheimer's Research & Therapy Pub Date : 2024-07-27 DOI:10.1186/s13195-024-01531-7
Anne-Brita Knapskog, Trine Holt Edwin, Per Magne Ueland, Arve Ulvik, Evandro Fei Fang, Rannveig Sakshaug Eldholm, Nathalie Bodd Halaas, Lasse M. Giil, Ingvild Saltvedt, Leiv Otto Watne, Mari Aksnes
{"title":"Sex-specific associations of kynurenic acid with neopterin in Alzheimer’s disease","authors":"Anne-Brita Knapskog, Trine Holt Edwin, Per Magne Ueland, Arve Ulvik, Evandro Fei Fang, Rannveig Sakshaug Eldholm, Nathalie Bodd Halaas, Lasse M. Giil, Ingvild Saltvedt, Leiv Otto Watne, Mari Aksnes","doi":"10.1186/s13195-024-01531-7","DOIUrl":null,"url":null,"abstract":"Sex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further. Here we investigate sex differences in cerebrospinal fluid concentrations of seven KP metabolites and sex-specific associations with established AD biomarkers and neopterin, an indicator of neuroinflammation. This study included 311 patients with symptomatic AD and 105 age-matched cognitively unimpaired (CU) controls, followed for up to 5 years. We found sex differences in KP metabolites in the AD group, with higher levels of most metabolites in men, while there were no sex differences in the CU group. In line with this, more KP metabolites were significantly altered in AD men compared to CU men, and there was a trend in the same direction in AD women. Furthermore, we found sex-specific associations between kynurenic acid and the kynurenic acid/quinolinic acid ratio with neopterin, but no sex differences in the associations between KP metabolites and clinical progression. In our cohort, sex differences in KP metabolites were restricted to AD patients. Our results suggest that dysregulation of the KP due to increased inflammation could contribute to higher AD risk in women.","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"43 1","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's Research & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13195-024-01531-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Sex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further. Here we investigate sex differences in cerebrospinal fluid concentrations of seven KP metabolites and sex-specific associations with established AD biomarkers and neopterin, an indicator of neuroinflammation. This study included 311 patients with symptomatic AD and 105 age-matched cognitively unimpaired (CU) controls, followed for up to 5 years. We found sex differences in KP metabolites in the AD group, with higher levels of most metabolites in men, while there were no sex differences in the CU group. In line with this, more KP metabolites were significantly altered in AD men compared to CU men, and there was a trend in the same direction in AD women. Furthermore, we found sex-specific associations between kynurenic acid and the kynurenic acid/quinolinic acid ratio with neopterin, but no sex differences in the associations between KP metabolites and clinical progression. In our cohort, sex differences in KP metabolites were restricted to AD patients. Our results suggest that dysregulation of the KP due to increased inflammation could contribute to higher AD risk in women.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
犬尿酸与阿尔茨海默病中蝶呤的性别特异性关联
神经炎症的性别差异可能会导致女性罹患阿尔茨海默病(AD)的风险增加,这为探索特定性别的阿尔茨海默病生物标志物提供了理论依据。在阿尔茨海默病中,犬尿氨酸途径(KP)的失调会导致神经炎症,有证据表明 KP 代谢存在性别差异。然而,KP代谢与AD和神经炎症生物标志物之间的性别特异性关联还需要进一步探讨。在此,我们研究了脑脊液中七种 KP 代谢物浓度的性别差异,以及与已确定的 AD 生物标志物和神经炎症指标蝶呤的性别特异性关联。这项研究纳入了311名有症状的注意力缺失症患者和105名年龄匹配的认知功能未受损(CU)对照组,并进行了长达5年的随访。我们发现,在注意力缺失症患者组中,KP代谢物存在性别差异,男性的大多数代谢物水平较高,而在认知功能障碍患者组中则没有性别差异。与此相符的是,与CU男性相比,AD男性有更多的KP代谢物发生了显著变化,而AD女性也有相同的趋势。此外,我们还发现犬尿苷酸和犬尿苷酸/喹啉酸比值与新蝶呤之间存在性别差异,但 KP 代谢物与临床进展之间没有性别差异。在我们的队列中,KP代谢物的性别差异仅限于AD患者。我们的研究结果表明,炎症加剧导致的KP失调可能会增加女性患AD的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Alzheimer's Research & Therapy
Alzheimer's Research & Therapy 医学-神经病学
CiteScore
13.10
自引率
3.30%
发文量
172
审稿时长
>12 weeks
期刊介绍: Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
期刊最新文献
Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer's disease, positive for plasma p-tau217. Frontotemporal structure preservation underlies the protective effect of lifetime intellectual cognitive reserve on cognition in the elderly. Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network flexibility among healthy older African Americans. Can the clinical sign "head-turning sign" and simple questions in "Neucop-Q" predict amyloid β pathology? A digitally supported multimodal lifestyle program to promote brain health among older adults (the LETHE randomized controlled feasibility trial): study design, progress, and first results.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1