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Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease

Mattsson-Carlgren, Niklas LU orcid ; Andersson, Emelie LU orcid ; Janelidze, Shorena LU ; Ossenkoppele, Rik LU ; Insel, Philip LU ; Strandberg, Olof LU ; Zetterberg, Henrik LU ; Rosen, Howard J. ; Rabinovici, Gil and Chai, Xiyun , et al. (2020) In Science Advances 6(16).
Abstract

The links between β-amyloid (Aβ) and tau in Alzheimer's disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau... (More)

The links between β-amyloid (Aβ) and tau in Alzheimer's disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
6
issue
16
article number
eaaz2387
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85083629574
  • pmid:32426454
ISSN
2375-2548
DOI
10.1126/sciadv.aaz2387
language
English
LU publication?
yes
id
1de8f059-c7df-4b20-bdf1-793d413a2308
date added to LUP
2020-05-20 13:56:28
date last changed
2024-05-30 15:50:32
@article{1de8f059-c7df-4b20-bdf1-793d413a2308,
  abstract     = {{<p>The links between β-amyloid (Aβ) and tau in Alzheimer's disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.</p>}},
  author       = {{Mattsson-Carlgren, Niklas and Andersson, Emelie and Janelidze, Shorena and Ossenkoppele, Rik and Insel, Philip and Strandberg, Olof and Zetterberg, Henrik and Rosen, Howard J. and Rabinovici, Gil and Chai, Xiyun and Blennow, Kaj and Dage, Jeffrey L. and Stomrud, Erik and Smith, Ruben and Palmqvist, Sebastian and Hansson, Oskar}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  number       = {{16}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1126/sciadv.aaz2387}},
  doi          = {{10.1126/sciadv.aaz2387}},
  volume       = {{6}},
  year         = {{2020}},
}