The association between APOE ε4 carrierships and the detection of amyloid positivity using an Alzheimer's disease proteomic blood test in asymptomatic Down syndrome

Authors

• Lubnaa Badriyyah Abdullah, University of North Texas Health Science CenterFollow
• Fan Zhang, University of North Texas Health Science Center
• Melissa Petersen, University of North Texas Health Science Center
• James Hall, University of North Texas Health Science Center
• Benjamin L. Handen, University of Pittsburgh
• Mark Mapstone, University of California Irvine
• Brad Christian, University of California Irvine
• Elizabeth Head, University of California Irvine
• Sigan Harley, University of Wisconsin-Madison
• Howard Andrews, Columbia University
• Joseph H. Lee, Columbia University
• Dana Tudorascu, University of California Irvine
• Christy Hom, University of California Irvine
• Shahid Zaman, University of Cambridge
• Adam M. Brickman, University of California Irvine
• Diana Rosas, Harvard University
• Annie Cohen, University of California Irvine
• Jordan P. Harp, University of KentuckyFollow
• Frederick Schmitt, University of Kentucky
• Lauren Ptomey, University of Kansas
• Jeffrey M. Burns, University of Pittsburgh
• Ira T. Lott, University of California Irvine
• Florence Lai, University of California Irvine
• Charles Laymon, University of Pittsburgh
• Carlos Cruchaga, Washington University School of Medicine in St. Louis
• Sid O'Bryant, University of Pittsburgh
• Beau M. Ances, University of California Irvine

Abstract

INTRODUCTION: This study evaluates plasma-based proteomic profiles for predicting amyloid positivity in adults with Down syndrome (DS) and examines the impact of apolipoprotein E ε4 (APOE ε4) on test performance. METHODS: Cross-sectional data from 290 adults with DS were analyzed using single molecule array (SIMOA) technology to measure plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181, and total tau. Amyloid burden was quantified using Pittsburgh Compound B and (18)F-florbetapir Aβ positron emission tomography. Support vector machine analyses were conducted with biomarkers as predictors and age, sex, and APOE ε4 carrier status as covariates. RESULTS: Age, GFAP, and NfL contributed the most to the model performance. The proteomic profile achieved an area under the curve (AUC) of 96% in models with and without APOE ε4. DISCUSSION: These findings suggest that plasma proteomic biomarkers can effectively identify amyloid positivity in adults with DS and may support clinical triage, monitoring, and selection for clinical trials, independent of APOE ε4 status.

Document Type

Article

Publication Date

4-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Digital Object Identifier (DOI)

10.1002/alz.71338

Archival?

Archival

Repository Citation

Abdullah, Lubnaa Badriyyah; Zhang, Fan; Petersen, Melissa; Hall, James; Handen, Benjamin L.; Mapstone, Mark; Christian, Brad; Head, Elizabeth; Harley, Sigan; Andrews, Howard; Lee, Joseph H.; Tudorascu, Dana; Hom, Christy; Zaman, Shahid; Brickman, Adam M.; Rosas, Diana; Cohen, Annie; Harp, Jordan P.; Schmitt, Frederick; Ptomey, Lauren; Burns, Jeffrey M.; Lott, Ira T.; Lai, Florence; Laymon, Charles; Cruchaga, Carlos; O'Bryant, Sid; and Ances, Beau M., "The association between APOE ε4 carrierships and the detection of amyloid positivity using an Alzheimer's disease proteomic blood test in asymptomatic Down syndrome" (2026). Neurology Faculty Publications. 148.
https://uknowledge.uky.edu/neurology_facpub/148