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CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease

Barthélemy, Nicolas R. ; Saef, Benjamin ; Li, Yan ; Gordon, Brian A. ; He, Yingxin ; Horie, Kanta ; Stomrud, Erik LU orcid ; Salvadó, Gemma LU ; Janelidze, Shorena LU and Sato, Chihiro , et al. (2023) In Nature Aging 3(4). p.391-401
Abstract

Cerebrospinal fluid (CSF) amyloid-β peptide (Aβ)42/Aβ40 and the concentration of tau phosphorylated at site 181 (p-tau181) are well-established biomarkers of Alzheimer’s disease (AD). The present study used mass spectrometry to measure concentrations of nine phosphorylated and five nonphosphorylated tau species and phosphorylation occupancies (percentage phosphorylated/nonphosphorylated) at ten sites. In the present study we show that, in 750 individuals with a median age of 71.2 years, CSF pT217/T217 predicted the presence of brain amyloid by positron emission tomography (PET) slightly better than Aβ42/Aβ40 (P = 0.02). Furthermore, for individuals with positive brain amyloid by PET (n = 263), CSF pT217/T217 was more strongly correlated... (More)

Cerebrospinal fluid (CSF) amyloid-β peptide (Aβ)42/Aβ40 and the concentration of tau phosphorylated at site 181 (p-tau181) are well-established biomarkers of Alzheimer’s disease (AD). The present study used mass spectrometry to measure concentrations of nine phosphorylated and five nonphosphorylated tau species and phosphorylation occupancies (percentage phosphorylated/nonphosphorylated) at ten sites. In the present study we show that, in 750 individuals with a median age of 71.2 years, CSF pT217/T217 predicted the presence of brain amyloid by positron emission tomography (PET) slightly better than Aβ42/Aβ40 (P = 0.02). Furthermore, for individuals with positive brain amyloid by PET (n = 263), CSF pT217/T217 was more strongly correlated with the amount of amyloid (Spearman’s ρ = 0.69) than Aβ42/Aβ40 (ρ = −0.42, P < 0.0001). In two independent cohorts of participants with symptoms of AD dementia (n = 55 and n = 90), CSF pT217/T217 and pT205/T205 were better correlated with tau PET measures than CSF p-tau181 concentration. These findings suggest that CSF pT217/T217 and pT205/T205 represent improved CSF biomarkers of amyloid and tau pathology in AD.

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type
Contribution to journal
publication status
published
subject
in
Nature Aging
volume
3
issue
4
pages
11 pages
publisher
Springer
external identifiers
  • scopus:85149806213
  • pmid:37117788
DOI
10.1038/s43587-023-00380-7
language
English
LU publication?
yes
id
49f65881-8c39-41d5-a05d-05d6905165bd
date added to LUP
2023-05-15 11:55:18
date last changed
2024-06-15 02:53:08
@article{49f65881-8c39-41d5-a05d-05d6905165bd,
  abstract     = {{<p>Cerebrospinal fluid (CSF) amyloid-β peptide (Aβ)42/Aβ40 and the concentration of tau phosphorylated at site 181 (p-tau181) are well-established biomarkers of Alzheimer’s disease (AD). The present study used mass spectrometry to measure concentrations of nine phosphorylated and five nonphosphorylated tau species and phosphorylation occupancies (percentage phosphorylated/nonphosphorylated) at ten sites. In the present study we show that, in 750 individuals with a median age of 71.2 years, CSF pT217/T217 predicted the presence of brain amyloid by positron emission tomography (PET) slightly better than Aβ42/Aβ40 (P = 0.02). Furthermore, for individuals with positive brain amyloid by PET (n = 263), CSF pT217/T217 was more strongly correlated with the amount of amyloid (Spearman’s ρ = 0.69) than Aβ42/Aβ40 (ρ = −0.42, P &lt; 0.0001). In two independent cohorts of participants with symptoms of AD dementia (n = 55 and n = 90), CSF pT217/T217 and pT205/T205 were better correlated with tau PET measures than CSF p-tau181 concentration. These findings suggest that CSF pT217/T217 and pT205/T205 represent improved CSF biomarkers of amyloid and tau pathology in AD.</p>}},
  author       = {{Barthélemy, Nicolas R. and Saef, Benjamin and Li, Yan and Gordon, Brian A. and He, Yingxin and Horie, Kanta and Stomrud, Erik and Salvadó, Gemma and Janelidze, Shorena and Sato, Chihiro and Ovod, Vitaliy and Henson, Rachel L. and Fagan, Anne M. and Benzinger, Tammie L.S. and Xiong, Chengjie and Morris, John C. and Hansson, Oskar and Bateman, Randall J. and Schindler, Suzanne E.}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{391--401}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1038/s43587-023-00380-7}},
  doi          = {{10.1038/s43587-023-00380-7}},
  volume       = {{3}},
  year         = {{2023}},
}