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
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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.
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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。
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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.
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