Journal Article Preprint Epublish 1 citation
PubMed: 40672486 DOI: 10.1101/2025.07.10.25331312
Plasma biomarkers, brain amyloid pathology, and cortical thickness in a diverse middle-aged community cohort: the HCP-CoBRA study.
medRxiv
Authors: Shayna T Brodman, Nicholas Heaton, Gallen Triana-Baltzer, Xuemei Zeng, Alexandra Gogola, M Ilyas Kamboh, Victor L Villemagne, Oscar L Lopez, Hartmuth Kolb, Rebecca A Deek, Ann D Cohen, Thomas K Karikari
Affiliations
- Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
- Department of Biostatistics and Health Data Science, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA.
- Neuroscience Biomarkers, Janssen Research & Development, La Jolla, CA, USA.
- Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh PA 15213, USA. Biofluid Biomarker Laboratory, Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh PA 15213, USA.
- Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
- Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
- Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh PA 15213, USA.
- Biofluid Biomarker Laboratory, Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh PA 15213, USA.
Abstract
INTRODUCTION
We evaluated plasma biomarker association with, and classification accuracies for, Aβ-PET and cortical thickness in the biracial HCP-CoBRA cohort (53% B/AA and 47% NHW).
METHODS
In n=218 participants (age 62 [range: 57-71] years, 65% female and 15% Aβ PET-positive), plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL, Aβ42/Aβ40) were compared to Aβ-PET and MRI neuroimaging indicators.
RESULTS
P-tau217 (Janssen and ALZpath [AUCs=0.915-0.919]) had high sensitivity and specificity (>85%) for Aβ-PET status. All biomarkers except p-tau231 ruled out Aβ-pathology (NPV>95%) but only Janssen p-tau217+ was good for confirmation (PPV=0.909). Plasma biomarkers performed poorly for predicting cortical thickness but were elevated according to joint Aβ-PET-neurodegeneration profiles. Biomarker accuracies for Aβ-PET positivity were unaffected by self-identified race, except ALZpath p-tau217(p=0.024). However, correlations with Aβ-PET varied by self-identified race.
DISCUSSION
P-tau217 is a promising tool for Alzheimer's disease-related Aβ pathology in older/middle-aged individuals. However, apparent race-related performances should be further studied.
MeSH
Neuroimaging, Brain, Pathology, Biomarkers, Aged, Amyloid, Plasma