Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology

• DOI: 10.1007/s00401-021-02275-6
• Publication Date: 2021-02-18T18:37:00Z
• Authors: Nicholas J. Ashton; Tharick A. Pascoal; Thomas K. Karikari; Andréa L. Benedet; Juan Lantero-Rodr...; Gunnar Brinkmalm; Anniina Snellman; Michael Schöll; Claire Troakes; Abdul Hye; Serge Gauthier; Eugeen Vanmechelen; Henrik Zetterberg; Pedro Rosa-Neto; Kaj Blennow
• Keywords: Neuropathology; Amyloid (mycology); Standardized uptake value

Abstract The quantification of phosphorylated tau in biofluids, either cerebrospinal fluid (CSF) or plasma, has shown great promise detecting Alzheimer’s disease (AD) pathophysiology. Tau at threonine 231 (p-tau231) is one such biomarker CSF but its usefulness as a blood currently unknown. Here, we developed an ultrasensitive Single molecule array (Simoa) for the plasma p-tau231 which was validated four independent cohorts ( n = 588) different settings, including full AD continuum and non-AD neurodegenerative disorders. Plasma able to identify patients with differentiate them from amyloid-β negative cognitively unimpaired (CU) older adults high accuracy (AUC 0.92–0.94). also distinguished disorders 0.93), well MCI 0.89). In neuropathology cohort, samples taken on avergae 4.2 years prior post-mortem very accurately identified comparison 0.99), this despite all being given dementia diagnosis during life. highly correlated p-tau231, pathology assessed by [ 18 F]MK-6240 positron emission tomography (PET), brain amyloidosis F]AZD469 PET. Remarkably, inflection point increasing function continuous PET standardized uptake value ratio, be earlier than standard thresholds positivity increase p-tau181. Furthermore, significantly increased quartiles 2–4, whereas p-tau217 p-tau181 only 3–4 4, respectively. Finally, differentiated individuals across entire Braak stage spectrum, staging 0 through I–II, not observed To conclude, novel assay identifies clinical stages equally p-tau181, increases earlier, already subtle deposition, threshold been attained, response early deposition. Thus, promising emerging potential facilitate trials vulnerable populations below apparent entorhinal