Longitudinal plasma Alzheimer’s disease biomarkers in an Alzheimer’s disease research center cohort suggest pTau181 as the most reliable plasma biomarker for brain Alzheimer’s pathology

Abstract

AbstractBackgroundBlood‐based biomarkers for the detection and longitudinal tracking of Alzheimer’s disease (AD) brain changes remains a goal for the field. In this study, we set out to evaluate Ab42/40, total tau, and pTau181 in our longitudinal clinical cohort. In most cases we have assessed five separate plasma samples spanning a seven‐year period. A subset of individuals had plasma samples aligning with an amyloid‐PET scan. A second subset of individuals cam to autopsy and had neuropathologic workup for correlation with the findings in the plasma biomarkers.MethodDuring their annual visits to the UK‐ADRC clinical core, participants had blood drawn and EDTA plasma was stored at ‐80oC in a standardized manner according to ADRC best practices. Quanterix Simoa assays were performed using Simoa Advantage assay kits and Quanterix Simoa HD‐1 and HD‐X instruments. Ab40, Ab42, total tau, and pTau181 analyses were performed. 96 participants had six annual plasma samples analyzed from an eight year period of collection. Of the samples assessed, 77 participants had plasma data aligning with an amyloid PET scan and 48 cases came to autopsy at the UK‐ADRC.ResultLooking at longitudinal plasma Total Tau, Ab40, and Ab42, Total Tau and the Ab42/40 ratio fluctuate significantly from year to year. In contrast, pTau181 does not show significant fluctuations year to year. Among those participants with an amyloid PET scan, pTau181 was significantly associated with amyloid SUVr in frontal, parietal, and anterior cingulate regions (R2 = 0.11 P<0.01; R2=0.12 P<0.01; R2=0.13 P<0.005 respectively). In contrast, we did not find statistically significant relationships between amyloid PET SUVr and plasma Ab42/40 ratio. Total tau showed modest associations with amyloid PET SUVr in the frontal, parietal, and anterior cingulate regions (R2=0.1 P<0.01; R2=0.05 P<0.05; R2=0.09 P<0.01 respectively). In our autopsy cases, we found a modest inverse relationship between brain amyloid load and plasma Ab42/40 ratio (P=0.05). Further analyses are required for the autopsy studies.ConclusionIn a community‐based cohort with longitudinal blood draws, pTau181 is a reliable, consistent plasma biomarker for AD pathology, showing more stability over time in participants than other candidate plasma biomarkers.