BRAIN: A JOURNAL OF NEUROLOGY

Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O, Mengel D, Walsh DM, Stomrud E, Dage JL and Hansson O.

Brain, awaa286

DOI:  https://doi.org/10.1093/brain/awaa286

Abstract

Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer’s disease. We studied 150 cognitively unimpaired participants and 100 patients with mild cognitive impairment in the Swedish BioFINDER study. P-tau217 was measured repeatedly for up to 6 years (median three samples per person, median time from first to last sample, 4.3 years). Preclinical (amyloid-β-positive cognitively unimpaired, n =62) and prodromal (amyloid-β-positive mild cognitive impairment, n =49) Alzheimer’s disease had accelerated p-tau217 compared to amyloid-β-negative cognitively unimpaired (β  =  0.56, P <0.001, using linear mixed effects models) and amyloid-β-negative mild cognitive impairment patients (β  =  0.67, P <0.001), respectively. Mild cognitive impairment patients who later converted to Alzheimer’s disease dementia (n =40) had accelerated p-tau217 compared to other mild cognitive impairment patients (β  =  0.79, P <0.001). P-tau217 did not change in amyloid-β-negative participants, or in patients with mild cognitive impairment who did not convert to Alzheimer’s disease dementia. For 80% power, 109 participants per arm were required to observe a slope reduction in amyloid-β-positive cognitively unimpaired (71 participants per arm in amyloid-β-positive mild cognitive impairment). Longitudinal increases in p-tau217 correlated with longitudinal worsening of cognition and brain atrophy. In summary, plasma p-tau217 increases during early Alzheimer’s disease and can be used to monitor disease progression.