期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 79, 期 2, 页码 671-681出版社
IOS PRESS
DOI: 10.3233/JAD-201167
关键词
Neurofilament light chain; proteomics; sensitivity; specificity; total-tau; trisomy 21
资金
- National Institutes on Aging [5U01AG 051406, U01AG051412]
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR001873]
- Alzheimer's Association [IIRG-08-90655]
- National Institute for Child Health and Human Development (NICHD) [P01HD035897]
- National Institute on Aging (NIA) [R01AG014673, R01A G058537, R01AG058252, R01AG051848]
- NYS through its office for People withDevelopmental Disabilities
- NIA [U24 AG21886]
This study investigated the diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau in distinguishing cognitive status among adults with Down syndrome (DS). The results indicated that Nf-L and total-tau could serve as useful biomarkers for both AD pathology and clinical status in DS, potentially becoming outcome measures in clinical trials for disease-modifying drugs in the future.
Background: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population. Objective: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults. Methods: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium - Down Syndrome. Results: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS. Conclusion: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.
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