Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment

Abstract

AbstractObjectivesWe sought to compare two of the most promising plasma biomarkers for Alzheimer disease (AD): pTau181 and pTau217.MethodspTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well characterized prospective multicentre BALTAZAR cohort of mild cognitive impairment (MCI) participants.ResultsAmong MCI participants, 55% were Aβ+ and 29% developed dementia due to AD. pTau181 and pTau217 were higher in the Aβ+ population with fold-change of 1.5 and 2.7 respectively. MCI that converted to AD also had higher levels than non-converters, with hazard ratios of 1.38 (1.26-1.51) for pTau181 compared to 8.22 (5.45-12.39) for pTau217. The AUC for predicting Aβ+ was 0.783 (95%CI: 0.721-0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95%CI: 0.868-0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex, and APOEε4 status, in a logistic model. Age, APOEε4 and renal dysfunction were associated with pTau levels, but the clinical performance of pTau217 was only marginally altered by these factors. Using a two cut-point approach, a 95% positive predictive value for Aβ+ corresponded to pTau217 > 0.8 pg/mL and a 95% negative predictive value at <0.23 pg/mL. At these two cut-points, the percentages of MCI conversion were 56.8% and 9.7% respectively, while the annual rates of decline in MMSE were −2.32 versus −0.65.ConclusionsPlasma pTau217 and pTau181 both correlate with AD, but the fold-change in pTau217 make it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia.