Mattsson-Carlgren, NiklasJanelidze, ShorenaBateman, Randall J.Smith, RubenStomrud, ErikSerrano, Geidy E.Reiman, Eric M.Palmqvist, SebastianDage, Jeffrey L.Beach, Thomas G.Hansson, Oskar2024-10-222024-10-222021Mattsson-Carlgren N, Janelidze S, Bateman RJ, et al. Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med. 2021;13(6):e14022. doi:10.15252/emmm.202114022https://hdl.handle.net/1805/44141Alzheimer's disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer's disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P-tau217, but P-tau217 was not elevated in patients with non-Alzheimer's disease tauopathies (N = 9). Several findings were replicated in a cohort with PET imaging ("BioFINDER-2", N = 426), where β-amyloid and tau PET were independently associated with P-tau217. P-tau217 concentrations correlated with β-amyloid PET (but not tau PET) in early disease stages and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 concentration is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.en-USAttribution 4.0 InternationalAlzheimer’s diseaseAmyloidPhosphorylated tauPlasmaTauArticle