{"title":"与传统的β -淀粉样蛋白和Tau蛋白生物标志物相比,评估氧化脂素对阿尔茨海默病连续体中认知测量和白质高信号的预测价值。","authors":"Alireza Shaabanpoor Haghighi, Mahsa Mayeli, Elham Ramezannezhad, Negin Pouroushaninia, Rezvan Barzegar Parizi, Mahtab Nourollahi-Foumeshi, Nasim Idelkhani, Zahra Dadjou, Niloofar Saeedipour, Negar Safaee, Homa Partoandaz, Mahan Shafie, Mohammad Sadeghi, Marjan Falahati","doi":"10.1007/s12035-025-05185-w","DOIUrl":null,"url":null,"abstract":"<p><p>Oxylipins are signaling molecules that result from the oxidation of long-chain polyunsaturated fatty acids, and they have been attracting attention due to their potential use as biomarkers for the early detection of Alzheimer's disease (AD) and other disorders. In contrast to beta-amyloid and tau protein biomarkers, we aimed to investigate the potential of oxylipins as an AD biomarker to predict cognitive measures. This study analyzed data from 703 participants (mean age 60 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We included 150 cognitively normal (CN) participants, 240 patients with early mild cognitive impairment (EMCI), 145 with late mild cognitive impairment (LMCI), 59 with subjetive memory complaints (SMC), and 109 with AD. Cognitive assessments were conducted using the clinical dementia rating scale (CDR), and cerebrospinal fluid (CSF) biomarkers (Aβ1-42 and p-tau181) were measured via the Luminex platform. Metabolite associations with CSF biomarkers were evaluated using random forest regression and linear regression models, with adjustments for age and sex and normalization for total intracranial volume (tICV). In the random forest regression model, Aβ42 was the most significant predictor for EMCI, while BSH_Sphingosine1P18.2 and BSL_GCDCA were significant for LMCI and MCI, respectively. Aβ42 appeared in SMC and CN but with lower significance than in EMCI. In CN, ASL_ResolvinE2 was most important. BSL_12_HETE was the strongest predictor for AD (R-squared = 0.199, metabolite-CSF R-squared = 0.024). Additionally, BSH_FA20.4_w6 (R-squared = 0.1772) outperformed CSF metabolites in EMCI detection, and BSH_Sphingosine1P16.1 (R-squared = 0.19) outperformed CSF metabolites in LMCI detection. Our findings suggest that select oxylipins may serve as predictive biomarkers of cognitive performance, although conventional CSF biomarkers remain superior for predicting the cognitive findings in the early stages.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14156-14166"},"PeriodicalIF":4.3000,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluating the Predictive Value of Oxylipins for Cognitive Measures and White Matter Hyperintensities in Alzheimer's Disease Continuum Compared to Conventional Beta‑amyloid and Tau Protein Biomarkers.\",\"authors\":\"Alireza Shaabanpoor Haghighi, Mahsa Mayeli, Elham Ramezannezhad, Negin Pouroushaninia, Rezvan Barzegar Parizi, Mahtab Nourollahi-Foumeshi, Nasim Idelkhani, Zahra Dadjou, Niloofar Saeedipour, Negar Safaee, Homa Partoandaz, Mahan Shafie, Mohammad Sadeghi, Marjan Falahati\",\"doi\":\"10.1007/s12035-025-05185-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Oxylipins are signaling molecules that result from the oxidation of long-chain polyunsaturated fatty acids, and they have been attracting attention due to their potential use as biomarkers for the early detection of Alzheimer's disease (AD) and other disorders. In contrast to beta-amyloid and tau protein biomarkers, we aimed to investigate the potential of oxylipins as an AD biomarker to predict cognitive measures. This study analyzed data from 703 participants (mean age 60 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We included 150 cognitively normal (CN) participants, 240 patients with early mild cognitive impairment (EMCI), 145 with late mild cognitive impairment (LMCI), 59 with subjetive memory complaints (SMC), and 109 with AD. Cognitive assessments were conducted using the clinical dementia rating scale (CDR), and cerebrospinal fluid (CSF) biomarkers (Aβ1-42 and p-tau181) were measured via the Luminex platform. Metabolite associations with CSF biomarkers were evaluated using random forest regression and linear regression models, with adjustments for age and sex and normalization for total intracranial volume (tICV). In the random forest regression model, Aβ42 was the most significant predictor for EMCI, while BSH_Sphingosine1P18.2 and BSL_GCDCA were significant for LMCI and MCI, respectively. Aβ42 appeared in SMC and CN but with lower significance than in EMCI. In CN, ASL_ResolvinE2 was most important. BSL_12_HETE was the strongest predictor for AD (R-squared = 0.199, metabolite-CSF R-squared = 0.024). Additionally, BSH_FA20.4_w6 (R-squared = 0.1772) outperformed CSF metabolites in EMCI detection, and BSH_Sphingosine1P16.1 (R-squared = 0.19) outperformed CSF metabolites in LMCI detection. Our findings suggest that select oxylipins may serve as predictive biomarkers of cognitive performance, although conventional CSF biomarkers remain superior for predicting the cognitive findings in the early stages.</p>\",\"PeriodicalId\":18762,\"journal\":{\"name\":\"Molecular Neurobiology\",\"volume\":\" \",\"pages\":\"14156-14166\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Neurobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12035-025-05185-w\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12035-025-05185-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Evaluating the Predictive Value of Oxylipins for Cognitive Measures and White Matter Hyperintensities in Alzheimer's Disease Continuum Compared to Conventional Beta‑amyloid and Tau Protein Biomarkers.
Oxylipins are signaling molecules that result from the oxidation of long-chain polyunsaturated fatty acids, and they have been attracting attention due to their potential use as biomarkers for the early detection of Alzheimer's disease (AD) and other disorders. In contrast to beta-amyloid and tau protein biomarkers, we aimed to investigate the potential of oxylipins as an AD biomarker to predict cognitive measures. This study analyzed data from 703 participants (mean age 60 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We included 150 cognitively normal (CN) participants, 240 patients with early mild cognitive impairment (EMCI), 145 with late mild cognitive impairment (LMCI), 59 with subjetive memory complaints (SMC), and 109 with AD. Cognitive assessments were conducted using the clinical dementia rating scale (CDR), and cerebrospinal fluid (CSF) biomarkers (Aβ1-42 and p-tau181) were measured via the Luminex platform. Metabolite associations with CSF biomarkers were evaluated using random forest regression and linear regression models, with adjustments for age and sex and normalization for total intracranial volume (tICV). In the random forest regression model, Aβ42 was the most significant predictor for EMCI, while BSH_Sphingosine1P18.2 and BSL_GCDCA were significant for LMCI and MCI, respectively. Aβ42 appeared in SMC and CN but with lower significance than in EMCI. In CN, ASL_ResolvinE2 was most important. BSL_12_HETE was the strongest predictor for AD (R-squared = 0.199, metabolite-CSF R-squared = 0.024). Additionally, BSH_FA20.4_w6 (R-squared = 0.1772) outperformed CSF metabolites in EMCI detection, and BSH_Sphingosine1P16.1 (R-squared = 0.19) outperformed CSF metabolites in LMCI detection. Our findings suggest that select oxylipins may serve as predictive biomarkers of cognitive performance, although conventional CSF biomarkers remain superior for predicting the cognitive findings in the early stages.
期刊介绍:
Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.