Soluble P‐tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. Issue 6 (5th May 2021)

• Record Type: Journal Article
• Authors: Mattsson‐Carlgren, Niklas; Janelidze, Shorena; Bateman, Randall J; Smith, Ruben; Stomrud, Erik; Serrano, Geidy E; Reiman, Eric M; Palmqvist, Sebastian; Dage, Jeffrey L; Beach, Thomas G; Hansson, Oskar
• Is Part Of: EMBO molecular medicine. Volume 13:Issue 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-05
• Subjects: Alzheimer's disease -- amyloid -- phosphorylated tau -- plasma -- tau; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.202114022
• Languages: English
• ISSNs: 1757-4676

Abstract

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. Synopsis: Plasma levels of phosphorylated tau, including P‐tau217, are elevated in Alzheimer's disease (AD). This study explores the underlying processes associated with the increased levels of plasma P‐tau217, using post‐mortem data and positron emission tomography (PET) of β‐amyloid and tau. Plasma P‐tau217 is independently associated with higher levels of both β‐amyloid pathology and tau pathology in the brain. The first changes in plasma P‐tau217 may reflect the early accumulation of β‐amyloid before there is widespread tau aggregation. Once tau aggregation reaches the neocortex, there is a strong correlation between plasma P‐tau217 and the amount of aggregated tau. Plasma P‐tau217 mediates the association between β‐amyloid accumulation and tau accumulation. Abstract : Plasma levels of phosphorylated tau, including P‐tau217, are elevated in Alzheimer's disease (AD). This study explores the underlying processes associated with the increased levels of plasma P‐tau217, using post‐mortem data and positron emission tomography (PET) of β‐amyloid and tau.