Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study

Date

2020-06-30

Authors

Petersen, Melissa E.
Zhang, Fan
Schupf, Nicole
Krinsky-McHale, Sharon J.
Hall, James R.
Mapstone, Mark
Cheema, Amrita
Silverman, Wayne
Lott, Ira
Rafii, Michael S.

ORCID

0000-0003-0582-5266 (O'Bryant, Sid E.)
0000-0002-3920-5877 (Petersen, Melissa E.)

Journal Title

Journal ISSN

Volume Title

Publisher

Wiley Periodicals, Inc.

Abstract

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.

Description

Keywords

Citation

Petersen, M. E., Zhang, F., Schupf, N., Krinsky-McHale, S. J., Hall, J., Mapstone, M., Cheema, A., Silverman, W., Lott, I., Rafii, M. S., Handen, B., Klunk, W., Head, E., Christian, B., Foroud, T., Lai, F., Rosas, H. D., Zaman, S., Ances, B. M., Wang, M. C., Tycko B, Lee JH, O'Bryant S; Alzheimer's Biomarker Consortium – Down Syndrome (ABC-DS) (2020). Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. Alzheimer's & dementia (Amsterdam, Netherlands), 12(1), e12039. https://doi.org/10.1002/dad2.12039