Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome
Por:
Petersen, ME, Rafii, MS, Zhang, F, Hall, J, Julovich, D, Ances, BM, Schupf, N, Krinsky-McHale, SJ, Mapstone, M, Silverman, W, Lott, I, Klunk, W, Head, E, Christian, B, Foroud, T, Lai, F, Rosas, HD, Zaman, S, Wang, MC, Tycko, B, Lee, JH, Handen, B, Hartley, S, Fortea, J, O'Bryant, S, Alzheimers Biomarker Consortium-Do
Publicada:
1 ene 2021
Resumen:
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.
Filiaciones:
Petersen, ME:
Univ North Texas, Dept Family Med, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Univ North Texas, Inst Translat Res, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Rafii, MS:
Univ Southern Calif, Keck Sch Med, Alzheimers Therapeut Res Inst ATRI, San Diego, CA USA
Zhang, F:
Univ North Texas, Dept Family Med, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Univ North Texas, Inst Translat Res, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Hall, J:
Univ North Texas, Inst Translat Res, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Univ North Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Ft Worth, TX 76107 USA
Julovich, D:
Univ North Texas, Inst Translat Res, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Univ North Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Ft Worth, TX 76107 USA
Ances, BM:
Washington Univ, Sch Med St Louis, Ctr Adv Med Neurosci, St Louis, MO 63110 USA
Schupf, N:
Columbia Univ, Taub Inst Res Alzheimers Dis, Irving Med Ctr, New York, NY USA
Columbia Univ, Aging Brain GH Sergievsky Ctr, Irving Med Ctr, New York, NY USA
Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA
Columbia Univ, Dept Neurol, Irving Med Ctr, Neurol Inst, New York, NY USA
Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA
Krinsky-McHale, SJ:
NYS Inst Basic Res Dev Disabil, Dept Psychol, Staten Isl, NY USA
Mapstone, M:
Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA
Silverman, W:
Univ Calif Irvine, Dept Pediat, Sch Med, Orange, CA 92668 USA
Lott, I:
Univ Calif Irvine, Dept Pediat, Sch Med, Orange, CA 92668 USA
Klunk, W:
Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA
Head, E:
Univ Calif Irvine, Dept Pathol, Irvine, CA 92717 USA
Christian, B:
Univ Wisconsin, Dept Med Phys & Psychiat, Madison, WI USA
Foroud, T:
Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA
Lai, F:
Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA
Rosas, HD:
Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA
Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA
Zaman, S:
Univ Cambridge, Sch Clin Med, Dept Psychiat, Cambridge, England
Cambridgeshire & Peterborough NHS Fdn Trust, Fulbourn Hosp, Cambridge, England
Wang, MC:
Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA
Tycko, B:
Columbia Univ, Dept Pathol & Cell Biol, Irving Med Ctr, New York, NY USA
Lee, JH:
Columbia Univ, Taub Inst Res Alzheimers Dis, Irving Med Ctr, New York, NY USA
Columbia Univ, Aging Brain GH Sergievsky Ctr, Irving Med Ctr, New York, NY USA
Handen, B:
Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA
Hartley, S:
Univ Wisconsin, Sch Human Ecol, Madison, WI USA
Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA
Fortea, J:
Fundacio Catalana Sindrome, Barcelona Med Ctr, Barcelona, Spain
Univ Autonoma Barcelona, Dept Neurol, St Pau Memory Unit, Hosp Santa Creu & St Pau,Biomed Res Inst St Pau, Barcelona, Spain
O'Bryant, S:
Univ North Texas, Inst Translat Res, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA
Univ North Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Ft Worth, TX 76107 USA
Green Accepted
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