The association between APOE 𝜀4 carrierships and the detection of amyloid positivity using an Alzheimer's disease proteomic blood test in asymptomatic Down syndrome
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71338
Authors: Lubnaa Badriyyah Abdullah, Fan Zhang, Melissa Petersen, James Hall, Benjamin L. Handen, Mark Mapstone, Brad Christian, Elizabeth Head, Sigan Harley, Howard Andrews, Joseph H Lee, Dana Tudorascu, Christy Hom, Shahid Zaman, Adam M Brickman, Diana Rosas, Annie Cohen, Jordan P Harp, Frederick Schmitt, Lauren Ptomey, Jeffrey M. Burns, Ira T Lott, Florence Lai, Charles Laymon, Carlos Cruchaga, Sid O'Bryant, Beau M. Ances
Institutions: University of North Texas, University of North Texas Health Science Center, University of Pittsburgh, University of California, Irvine, University of Wisconsin–Madison, Columbia University, University of Cambridge, Harvard University, Massachusetts General Hospital, University of Kentucky, University of Kansas Medical Center, Washington University in St. Louis
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W7153472817