Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology

Abstract

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Thereafter, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n=388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a novel peripherally accessible biomarker of AD pathophysiology.

Novel ultrasensitive immunoassay for the selective quantification of tau oligomers and related soluble aggregates

“…While multiple tau‐based immunoassays for the measurement of phosphorylated and non‐phosphorylated forms of tau 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 as well as other assays that use the same homogenous assay approach employed herein 38 exist, assays specifically for oligomeric and soluble aggregated forms of tau are lacking. Moreover, the specificity of several so‐called tau oligomer or fibril antibodies and assays have been called into question.…”