Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration
IntroductionCirculating very-long-chain saturated fatty acids (VLSFAs) may attenuate age-related cognitive decline, but their direct association with neurodegeneration biomarkers and the underlying mechanisms remain unclear.MethodsThis cross-sectional study examined associations between circulating...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Human Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnhum.2025.1598495/full |
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| author | Lumi Zhang Duanbin Li Na Zhao Guoping Peng |
| author_facet | Lumi Zhang Duanbin Li Na Zhao Guoping Peng |
| author_sort | Lumi Zhang |
| collection | DOAJ |
| description | IntroductionCirculating very-long-chain saturated fatty acids (VLSFAs) may attenuate age-related cognitive decline, but their direct association with neurodegeneration biomarkers and the underlying mechanisms remain unclear.MethodsThis cross-sectional study examined associations between circulating fatty acid profiles, neurodegeneration (assessed by serum neurofilament light chain, NfL), cognitive function, and hypertension in 1,677 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. Advanced statistical methods including weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), quantile g-computation (Qgcomp), and formal mediation analyses were employed.ResultsThe VLSFA mixture demonstrated significant inverse associations with serum NfL (β = −0.044, 95% CI: -0.076, -0.011) and the prevalence of hypertension (OR = 0.788, 95% CI: 0.672, 0.923). This association with NfL was non-linear, exhibiting a more pronounced protective effect at lower VLSFA concentrations. Higher VLSFA levels were significantly correlated with better cognitive performance, particularly in processing speed (Digit-Symbol Substitution Test) and memory (delayed recall). Hypertension was positively associated with NfL (β=4.133, 95% CI: 1.705, 6.562), an effect driven primarily by systolic blood pressure. Mediation analysis revealed that hypertension accounted for approximately 15–20% of the total association between VLSFAs and NfL.DiscussionCirculating VLSFAs are inversely associated with the neurodegeneration biomarker NfL and positively correlated with cognitive performance. This neuroprotective association appears to be partially mediated by blood pressure regulation pathways. These findings identify VLSFAs as a potential therapeutic target, warranting further longitudinal and interventional studies to confirm their role in mitigating neurodegeneration. |
| format | Article |
| id | doaj-art-6fd4abf82cea42ceb8cdacbd1d70f67e |
| institution | DOAJ |
| issn | 1662-5161 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Human Neuroscience |
| spelling | doaj-art-6fd4abf82cea42ceb8cdacbd1d70f67e2025-08-20T03:22:03ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612025-06-011910.3389/fnhum.2025.15984951598495Serum lipidomic analysis identifies potential therapeutic targets for neurodegenerationLumi Zhang0Duanbin Li1Na Zhao2Guoping Peng3Department of Neurology, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, ChinaDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Neurology, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, ChinaDepartment of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaIntroductionCirculating very-long-chain saturated fatty acids (VLSFAs) may attenuate age-related cognitive decline, but their direct association with neurodegeneration biomarkers and the underlying mechanisms remain unclear.MethodsThis cross-sectional study examined associations between circulating fatty acid profiles, neurodegeneration (assessed by serum neurofilament light chain, NfL), cognitive function, and hypertension in 1,677 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. Advanced statistical methods including weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), quantile g-computation (Qgcomp), and formal mediation analyses were employed.ResultsThe VLSFA mixture demonstrated significant inverse associations with serum NfL (β = −0.044, 95% CI: -0.076, -0.011) and the prevalence of hypertension (OR = 0.788, 95% CI: 0.672, 0.923). This association with NfL was non-linear, exhibiting a more pronounced protective effect at lower VLSFA concentrations. Higher VLSFA levels were significantly correlated with better cognitive performance, particularly in processing speed (Digit-Symbol Substitution Test) and memory (delayed recall). Hypertension was positively associated with NfL (β=4.133, 95% CI: 1.705, 6.562), an effect driven primarily by systolic blood pressure. Mediation analysis revealed that hypertension accounted for approximately 15–20% of the total association between VLSFAs and NfL.DiscussionCirculating VLSFAs are inversely associated with the neurodegeneration biomarker NfL and positively correlated with cognitive performance. This neuroprotective association appears to be partially mediated by blood pressure regulation pathways. These findings identify VLSFAs as a potential therapeutic target, warranting further longitudinal and interventional studies to confirm their role in mitigating neurodegeneration.https://www.frontiersin.org/articles/10.3389/fnhum.2025.1598495/fullVLSFANfLneurodegenerationhypertensionNHANES |
| spellingShingle | Lumi Zhang Duanbin Li Na Zhao Guoping Peng Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration Frontiers in Human Neuroscience VLSFA NfL neurodegeneration hypertension NHANES |
| title | Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration |
| title_full | Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration |
| title_fullStr | Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration |
| title_full_unstemmed | Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration |
| title_short | Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration |
| title_sort | serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration |
| topic | VLSFA NfL neurodegeneration hypertension NHANES |
| url | https://www.frontiersin.org/articles/10.3389/fnhum.2025.1598495/full |
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