Plasma p-tau231, p-tau181, PET biomarkers and cognitive change in older adults
Annals of Neurology | January 27, 2022
Meyer PF, Ashton NJ, Karikari TK, Strikwerda-Brown C, Köbe T, Gonneaud J, Pichet Binette A, Ozlen H, Yakoub Y, Simrén J, Pannee J, Lantero-Rodriguez J, Labonté A, Baker SL, Schöll M, Vanmechelen E, Breitner JCS, Zetterberg H, Blennow K, Poirier J and Villeneuve S
Ann Neurol. 2022
To evaluate novel plasma p-tau231, p-tau181 as well as Aβ40 and Aβ42 assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults.
In a cohort of 244 older adults at risk of AD owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231, p-tau181), Aβ40 and Aβ42 with immunoprecipitation mass spectrometry, and Simoa NfL. A subset of 129 participants underwent amyloid-β (18F-NAV4694) and tau (18F-flortaucipir) PET assessments. We investigated plasma biomarker associations with Aβ and tau PET at the global and voxel level and tested plasma biomarker combinations for improved detection of Aβ-PET positivity. We also investigated associations with 8-year cognitive change.
Plasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma Aβ42/40 explained more variance in global Aβ-PET binding than Aβ42 alone. P-tau231 also showed strong and widespread associations with cortical Aβ-PET binding. Combining Aβ42/40 with p-tau231 or p-tau181 allowed for good distinction between Aβ-negative and -positive participants (AUC range 0.81-0.86). Individuals with low plasma Aβ42/40 and high p-tau experienced faster cognitive decline.
Plasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in pre-symptomatic individuals. The combination of p-tau and Aβ42/40 biomarkers detected early AD pathology and cognitive decline. Such markers could be used as pre-screening tools to reduce the cost of prevention trials.