TY - JOUR
T1 - Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma
T2 - An Alzheimer's Biomarker Consortium–Down Syndrome (ABC–DS) study
AU - the Alzheimer's Biomarker Consortium – Down Syndrome (ABC-DS)
AU - Petersen, Melissa E.
AU - Zhang, Fan
AU - Schupf, Nicole
AU - Krinsky-McHale, Sharon J.
AU - Hall, James
AU - Mapstone, Mark
AU - Cheema, Amrita
AU - Silverman, Wayne
AU - Lott, Ira
AU - Rafii, Michael S.
AU - Handen, Benjamin
AU - Klunk, William
AU - Head, Elizabeth
AU - Christian, Brad
AU - Foroud, Tatiana
AU - Lai, Florence
AU - Rosas, H. Diana
AU - Zaman, Shahid
AU - Ances, Beau M.
AU - Wang, Mei Cheng
AU - Tycko, Benjamin
AU - Lee, Joseph H.
AU - O'Bryant, Sid
AU - Aizenstein, Howard J.
AU - Andrews, Howard F.
AU - Bell, Karen
AU - Birn, Rasmus M.
AU - Brickman, Adam M.
AU - Bulova, Peter
AU - Cheema, Amrita
AU - Chen, Kewei
AU - Christian, Bradley T.
AU - Clare, Isabel
AU - Clark, Lorraine
AU - Cohen, Ann D.
AU - Constantino, John N.
AU - Doran, Eric W.
AU - Fagan, Anne
AU - Feingold, Eleanor
AU - Foroud, Tatiana M.
AU - Handen, Benjamin L.
AU - Hartley, Sigan L.
AU - Henson, Rachel
AU - Hom, Christy
AU - Honig, Lawrence
AU - Ikonomovic, Milos D.
AU - Johnson, Sterling C.
AU - Jordan, Courtney
AU - Kamboh, M. Ilyas
AU - Keator, David
N1 - Funding Information:
The Alzheimer's Biomarkers Consortium–Down Syndrome (ABC–DS) project is a longitudinal study of cognition and blood‐based, genetic, and imaging biomarkers of Alzheimer's disease. This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. This work was also supported by grant IIRG‐08‐90655 from the Alzheimer's Association (Schupf, O'Bryant) and by additional grants P01HD035897 (Silverman) from National Institute for Child Health and Human Development (NICHD), and R01AG014673 (Schupf), R01AG058537 (O'Bryant), R01AG058252 (O'Bryant) and R01AG051848 (O'Bryant) from National Institute on Aging (NIA), and by NYS through its office for People with Developmental Disabilities. We thank the ABC–DS study participants and the ABC–DS research and support staff for their contributions to this study.
Funding Information:
Samples from the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the NIA, were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible.
Publisher Copyright:
© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association
PY - 2020
Y1 - 2020
N2 - Introduction: Previously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS). Methods: Data were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium–Down Syndrome (ABC–DS). Results: Distinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A, and FABP3 correlated fractions at r2> = 0.90. Discussion: Proteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD.
AB - Introduction: Previously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS). Methods: Data were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium–Down Syndrome (ABC–DS). Results: Distinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A, and FABP3 correlated fractions at r2> = 0.90. Discussion: Proteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD.
UR - http://www.scopus.com/inward/record.url?scp=85100485803&partnerID=8YFLogxK
U2 - 10.1002/dad2.12039
DO - 10.1002/dad2.12039
M3 - Article
C2 - 32626817
AN - SCOPUS:85100485803
SN - 2352-8729
VL - 12
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
IS - 1
M1 - e12039
ER -