Plasma biomarkers, brain amyloid pathology, and cortical thickness in a diverse middle-aged community cohort: the HCP-CoBRA study

  1. Shayna T. Brodman
  2. Nicholas Heaton
  3. Gallen Triana-Baltzer
  4. Xuemei Zeng
  5. Alexandra Gogola
  6. M. Ilyas Kamboh
  7. Victor L. Villemagne
  8. Oscar L. Lopez
  9. Hartmuth Kolb
  10. Rebecca A. Deek
  11. Ann D. Cohen
  12. Thomas K. Karikari
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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.

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