AI Article Synopsis
- Alzheimer's disease (AD) involves the buildup of amyloid-beta (Aβ) plaques and neurofibrillary tangles, and newly approved treatments stress the importance of early detection of Aβ abnormalities in non-demented individuals for timely intervention.
- The study analyzed cerebrospinal fluid (CSF) proteins from 474 non-demented participants to find biomarkers linked to Aβ positivity, identifying three key proteins: APOE, CHI3L1, and SMOC1 using LASSO regression.
- Among the identified proteins, SMOC1 was found to be a strong predictor of Aβ positivity and its progression, suggesting it could serve as a valuable biomarker in AD diagnosis
Article 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.
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| http://dx.doi.org/10.14283/jpad.2024.129 | DOI Listing |
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