Moderator of 1 Session
Presenter of 2 Presentations
MasterClass 2: Employing Validated Diagnostic Tools to Optimize the Early Biomarker-Based Diagnosis of Alzheimer’s Disease
THE CROSS-SECTIONAL AND LONGITUDINAL ASSOCIATION OF PLASMA P-TAU181, P-TAU217 AND P-TAU231 WITH ALZHEIMER’S DISEASE PHENOTYPES
Abstract
Aims
Plasma biomarkers, namely phosphorylated tau (p-tau), have proven to be highly valuable to identify Alzheimer’s disease (AD) pathology in presence of cognitive decline. In addition, both p-tau181 and p-tau217 have been shown to be effective in categorizing those who are at high-risk for AD. Recently, p-tau231 has also been shown to be an accurate measure of AD pathology and postulated to be elevated earlier in the AD continuum. This is the first description of plasma p-tau231 in the BioFINDER cohort(s) and compares the cross-sectional and longitudinal association of three plasma p-tau biomarkers with AD phenotypes.
Methods
In both BioFINDER-1 and BioFINDER-2 cohorts, plasma p-tau181 and plasma p-tau231 were quantified by single molecular arrays (Simoa) developed at the University of Gothenburg, Sweden. Plasma p-tau217 was quantified by the Meso Scale Discovery (MSD) by Eli Lily. Aβ status was quantified by both CSF Aβ42/Aβ40 or Aβ-PET.
Results
In BioFINDER-2, plasma p-tau231 was elevated in Aβ+ individuals compared to Aβ– (AUC=0.85) and a stepwise increase of p-tau231 was observed throughout the AD continuum. At dementia stages, however, plasma p-tau217 exhibited the largest fold-changes between Aβ+ and Aβ– groups. In the preclinical stage, both p-tau231 and p-tau217 outperformed p-tau181 to indicate Aβ+ (DeLong, P<0.01) and both biomarkers were equally suitable (AUC=0.74–76) to identify the earliest Aβ accumulators (CSF+/PET-).
Conclusions
P-tau231 has high accuracy to determine AD pathology. However, in considering other p-tau biomarkers, it performs best preclinically to identify earliest Aβ accumulators. Further analysis will present the longitudinal trajectories of plasma p-tau181, p-tau217 and p-tau231 in BioFINDER-1.