{"title":"Unveiling Potential Biomarkers in Cerebrospinal Fluid for Amyloid Pathological Positivity in Non-Demented Individuals","authors":"F. Meng, Xi Zhang","doi":"10.14283/jpad.2024.129","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and neurofibrillary tangles. The recent approval of anti-amyloid therapeutic medications highlights the crucial need for early detection of Aβ pathological abnormalities in individuals without dementia to facilitate timely intervention and treatment.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The primary aim of this study was to identify cerebrospinal fluid (CSF) biomarkers strongly associated with Aβ pathological positivity in a non-demented cohort and evaluate their clinical values.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A comprehensive analysis was conducted on 51 CSF proteins (excluding Aβ42, pTau, and Tau) obtained from 474 non-demented participants sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. By utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, we identified potential proteins indicative of Aβ pathological positivity and evaluated their performance in tracking longitudinal pathological progression.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our LASSO analysis unveiled three candidates: apolipoprotein E (APOE), chitinase-3-like protein 1 (CHI3L1), and SPARC-related modular calcium-binding protein 1 (SMOC1). While SMOC1 did not correlate with Aβ42-related cognitive alterations, it displayed better abilities in discriminating both CSF-Aβ positivity and Aβ-positron emission tomography (PET) positivity than the other two candidates. It could precisely predict longitudinal Aβ-PET status conversion. Notably, SMOC1 was the only protein showing associations with longitudinal Aβ-PET trajectory and enhancing the diagnostic accuracy of Aβ42. The assessment of combined Aβ42 and SMOC1 yielded valuable clinical insights.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings elucidated SMOC1 as a potential biomarker for detecting Aβ abnormalities. Aβ42 combining SMOC1 offered critical implications in AD pathological diagnosis and management.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Prevention of Alzheimer's Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14283/jpad.2024.129","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BUSINESS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and neurofibrillary tangles. The recent approval of anti-amyloid therapeutic medications highlights the crucial need for early detection of Aβ pathological abnormalities in individuals without dementia to facilitate timely intervention and treatment.
Objective
The primary aim of this study was to identify cerebrospinal fluid (CSF) biomarkers strongly associated with Aβ pathological positivity in a non-demented cohort and evaluate their clinical values.
Methods
A comprehensive analysis was conducted on 51 CSF proteins (excluding Aβ42, pTau, and Tau) obtained from 474 non-demented participants sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. By utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, we identified potential proteins indicative of Aβ pathological positivity and evaluated their performance in tracking longitudinal pathological progression.
Results
Our LASSO analysis unveiled three candidates: apolipoprotein E (APOE), chitinase-3-like protein 1 (CHI3L1), and SPARC-related modular calcium-binding protein 1 (SMOC1). While SMOC1 did not correlate with Aβ42-related cognitive alterations, it displayed better abilities in discriminating both CSF-Aβ positivity and Aβ-positron emission tomography (PET) positivity than the other two candidates. It could precisely predict longitudinal Aβ-PET status conversion. Notably, SMOC1 was the only protein showing associations with longitudinal Aβ-PET trajectory and enhancing the diagnostic accuracy of Aβ42. The assessment of combined Aβ42 and SMOC1 yielded valuable clinical insights.
Conclusion
Our findings elucidated SMOC1 as a potential biomarker for detecting Aβ abnormalities. Aβ42 combining SMOC1 offered critical implications in AD pathological diagnosis and management.
期刊介绍：
The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
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