Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease
(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.
(Less)
- author
- organization
- publishing date
- 2020
- 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
-
- pmid:32426454
- scopus:85083629574
- 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
- 2024-09-19 22:27:00
@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}}, }