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

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.

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Publication Details

Journal
Alzheimer s & Dementia
Published
2026-04-01
DOI
https://doi.org/10.1002/alz.71338
Primary Topic
Down syndrome and intellectual disability research
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Frederick A. Schmitt, J. Camille Hall, Christy Hom, Brad T. Christian et al.
Alzheimer s & Dementia
Down syndrome and intellectual disability research
article

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

Frederick A. Schmitt, J. Camille Hall, Christy Hom, Brad T. Christian, Lubnaa Abdullah, Jeffrey Murray Burns, Florence Lai, H Andrews, Diana Rosas, Joseph H Lee, Melissa Petersen, Jordan P Harp, Sid O'Bryant, Elizabeth Head, Sigan Harley, Carlos Cruchaga, Ira T Lott, Lauren Ptomey, Fan Zhang, Shahid Zaman, Dana Tudorascu, Adam M Brickman, Mark Mapstone, Beau M. Ances, Charles Laymon, Benjamin L. Handen
article en

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.

Alzheimer s & DementiaVol. 22(4)
University of North Texas (US), University of Wisconsin–Madison (US), University of Kentucky (US), University of North Texas Health Science Center (US), University of Pittsburgh (US), University of California, Irvine (US), Washington University in St. Louis (US), University of Cambridge (GB), Massachusetts General Hospital (US), University of California, Irvine Medical Center (US), Texas Health Harris Methodist Hospital Fort Worth (US), University of Kansas Medical Center (US), Irvine University (US), Columbia University (US)
National Institutes of Health, National Institute on Aging, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Good health and well-being
Openalex Percentile: Top 22%
Down syndrome and intellectual disability research
DOIOpen Access PDFOpenAlex
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