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

Mattsson-Carlgren, Niklas LU orcid ; Janelidze, Shorena LU ; Bateman, Randall J. ; Smith, Ruben LU ; Stomrud, Erik LU orcid ; Serrano, Geidy E. ; Reiman, Eric M. ; Palmqvist, Sebastian LU orcid ; Dage, Jeffrey L. and Beach, Thomas G. , et al. (2021) In EMBO Molecular Medicine 13(6).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, amyloid, phosphorylated tau, plasma, tau
in
EMBO Molecular Medicine
volume
13
issue
6
article number
e14022
publisher
Wiley-Blackwell
external identifiers
  • pmid:33949133
  • scopus:85105072472
ISSN
1757-4676
DOI
10.15252/emmm.202114022
language
English
LU publication?
yes
id
def5f9b8-9e93-4e4b-9f93-4d1e6a27cd69
date added to LUP
2021-05-31 12:11:17
date last changed
2024-06-15 11:46:28
@article{def5f9b8-9e93-4e4b-9f93-4d1e6a27cd69,
  abstract     = {{<p>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.</p>}},
  author       = {{Mattsson-Carlgren, Niklas and Janelidze, Shorena and Bateman, Randall J. and Smith, Ruben and Stomrud, Erik and Serrano, Geidy E. and Reiman, Eric M. and Palmqvist, Sebastian and Dage, Jeffrey L. and Beach, Thomas G. and Hansson, Oskar}},
  issn         = {{1757-4676}},
  keywords     = {{Alzheimer’s disease; amyloid; phosphorylated tau; plasma; tau}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau}},
  url          = {{http://dx.doi.org/10.15252/emmm.202114022}},
  doi          = {{10.15252/emmm.202114022}},
  volume       = {{13}},
  year         = {{2021}},
}