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COMPARISON OF BLOOD-BASED PTAU181 AND PTAU231 AS BIOMARKERS OF CLINICAL AND ASYMPTOMATIC ALZHEIMER'S DISEASE WHEN MEASURED BY NOVEL SIMOA ASSAYS
Abstract
Aims
While blood-based phosphorylated tau (pTau)181, pTau217 and pTau231 show equivalent diagnostic utility for Alzheimer’s Disease (AD), temporal differences have been observed in the AD continuum. We compare the diagnostic performance of prototype pTau181 and pTau231 assays in clinical and asymptomatic AD stages as well as the relationship of pTau species with amyloid burden.
Methods
Plasma pTau181 and pTau231 were measured using novel, highly-specific SIMOA assays in a memory-clinic recruited cohort of biomarker-proven AD patients (44 AD, 40 age-matched spouse controls (SC), median 74 years) as well as in 151 cognitively unimpaired (CU) elderly of the Flemish Prevent AD cohort KU Leuven (F-PACK, median 70 years) of which 38 were amyloid-PET positive (CL > 23.5). Both assays use the same detector antibody and synthetic peptide calibrator in addition to capture antibodies ADx253 and ADx252, which are highly specific for the targeted phospho-site. In contrast to previous pTau181 assays, the novel pTau181 assay showed no cross-reactivity with pTau175. Amyloid PET was obtained from all F-PACK participants.
Results
Plasma pTau181 could more reliably distinguish AD patients from SC (AUC=0.98 [ 0.95-1]) than plasma pT231 (AUC=0.74 [0.63-0.85], P(diff)<0.0001). Within the asymptomatic phase (F-PACK), pTau181 (AUC=0.84 [0.76-0.92]) more accurately predicted amyloid-PET status than pT231 (AUC=0.63 [0.53-0.72], P(diff)<0.0001). Besides, plasma pTau181 was associated with the presence of widespread cerebral amyloid burden (Figure 1A), while pTau231 was not (Figure 1B).
Conclusions
When measured with highly-specific assays, plasma pT181 seems to show a better performance than pTau231 in both the clinical and asymptomatic phase of AD.