EMBO Molecular Medicine | July 13, 2021

Ossenkoppele R, Reimand J, Smith R, Leuzy A, Strandberg O, Palmqvist S, Stomrud E, Zetterberg H, Scheltens P, Dage JL, Bouwman F, Blennow K, Mattsson-Carlgren N, Janelidze S and Hansson O

EMBO molecular medicine. 2021:e14398

DOI: https://doi.org/10.15252/emmm.202114398

This study was performed using a Simoa Homebrew assay.

Abstract

PET, CSF and plasma biomarkers of tau pathology may be differentially associated with Alzheimer’s disease (AD)-related demographic, cognitive, genetic and neuroimaging markers. We examined 771 participants with normal cognition, mild cognitive impairment or dementia from BioFINDER-2 (n = 400) and ADNI (n = 371). All had tau-PET ([¹⁸F]RO948 in BioFINDER-2, [¹⁸F]flortaucipir in ADNI) and CSF p-tau181 biomarkers available. Plasma p-tau181 and plasma/CSF p-tau217 were available in BioFINDER-2 only. Concordance between PET, CSF and plasma tau biomarkers ranged between 66 and 95%. Across the whole group, ridge regression models showed that increased CSF and plasma p-tau181 and p-tau217 levels were independently of tau PET associated with higher age, and APOEɛ4-carriership and Aβ-positivity, while increased tau-PET signal in the temporal cortex was associated with worse cognitive performance and reduced cortical thickness. We conclude that biofluid and neuroimaging markers of tau pathology convey partly independent information, with CSF and plasma p-tau181 and p-tau217 levels being more tightly linked with early markers of AD (especially Aβ-pathology), while tau-PET shows the strongest associations with cognitive and neurodegenerative markers of disease progression.