Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

Niklas Mattsson-Carlgren, Shorena Janelidze, Randall J. Bateman, Ruben Smith, Erik Stomrud, Geidy E. Serrano, Eric M. Reiman, Sebastian Palmqvist, Jeffrey L. Dage, Thomas G. Beach, Oskar Hansson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Alzheimer’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.

Original languageEnglish
Article numbere14022
JournalEMBO Molecular Medicine
Volume13
Issue number6
DOIs
StatePublished - Jun 7 2021

Keywords

  • Alzheimer’s disease
  • amyloid
  • phosphorylated tau
  • plasma
  • tau

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