eBioMedicine | February 6, 2022

Tissot C, Therriault J, Kunach P, L Benedet A, Pascoal TA, Ashton NJ, Karikari TK, Servaes S, Lussier FZ, Chamoun M, Tudorascu DL, Stevenson J, Rahmouni N, Poltronetti NM, Pallen V, Bezgin G, Kang MS, Mathotaarachchi SS, Wang Y-T, Fernandez Arias J, Ferreira PCL, Ferrari-Souza JP, Vanmechelen E, Blennow K, Zetterberg H, Gauthier S and Rosa-Neto P

eBioMedicine. 2022;76:103837

https://doi.org/10.1016/j.ebiom.2022.103837

This study was performed using Simoa Homebrew assay(s).

Abstract

Background

Tau in Alzheimer’s disease (AD) is assessed via cerebrospinal fluid (CSF) and Positron emission tomography (PET). Novel methods to detect phosphorylated tau (pTau) in blood have been recently developed. We aim to investigate agreement of tau status as determined by [¹⁸F]MK6240 tau-PET, plasma pTau181 and pTau231.

Methods

We assessed cognitively unimpaired young, cognitively unimpaired, mild cognitive impairment and AD individuals with [¹⁸F]MK6240, plasma pTau181, pTau 231, [¹⁸F]AZD4694 amyloid-PET and MRI. A subset underwent CSF assessment.

We conducted ROC curves to obtain cut-off values for plasma pTau epitopes. Individuals were categorized as positive or negative in all biomarkers. We then compared the distribution among concordant and discordant groups in relation to diagnosis, Aβ status, APOEε4 status, [¹⁸F]AZD4694 global SUVR, hippocampal volume and CSF pTau181.

Findings

The threshold for positivity was 15.085 pg/mL for plasma pTau181 and 17.652 pg/mL for plasma pTau231. Most individuals had concordant statuses, however, 18% of plasma181/PET, 26% of plasma231/PET and 25% of the pTau231/pTau181 were discordant. Positivity to at least one biomarker was often accompanied by diagnosis of cognitive impairment, Aβ positivity, APOEε4 carriership, higher levels of [¹⁸F]AZD4694 global SUVR, hippocampal atrophy and CSF pTau181.

Interpretation

Plasma pTau181, pTau231 and [¹⁸F]MK6240 seem to reflect different stages of tau progression. Plasma biomarkers can be useful in the context of diagnostic information and clinical trials, to evaluate the disease stage. Moreover, they seem to confidently evaluate tau-PET positivity.