Cellular localization of p-tau217 in brain and its association with p-tau217 plasma levels

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Abstract

Recent studies highlight phosphorylated tau (p-tau) at threonine tau 217 (p-tau217) as a new promising plasma biomarker for pathological changes implicated in Alzheimer’s disease (AD), but the specific brain pathological events related to the alteration in p-tau217 plasma levels are still largely unknown. Using immunostaining techniques of postmortem AD brain tissue, we show that p-tau217 is found in neurofibrillary tangles (NFTs) and neuropil threads that are also positive for p-tau181, 202, 202/205, 231, and 369/404. The p-tau217, but not the other five p-tau variants, was also prominently seen in vesicles structure positive for markers of granulovacuolar degeneration bodies and multi-vesicular bodies. Further, individuals with a high likelihood of AD showed significantly higher p-tau217 area fraction in 4 different brain areas (entorhinal cortex, inferior temporal gyrus, and superior frontal gyrus) compared to those with Primary age related tauopathy or other non-AD tauopathies. The p-tau217 area fraction correlated strongly with total amyloid-beta (Aβ) and NFT brain load when the whole group was analyzed. Finally, the mean p-tau217 area fraction correlated significantly with p-tau217 concentrations in antemortem collected plasma specifically in individuals with amyloid plaques and not in those without amyloid plaques. These studies highlight differences in cellular localization of different p-tau variants and suggest that plasma levels of p-tau217 reflect an accumulation of p-tau217 in presence of Aβ plaque load.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40478-021-01307-2.

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Author and article information

Contributors

Malin Wennström:

ORCID: http://orcid.org/0000-0002-9957-1801

malin.wennstrom@med.lu.se

Oskar Hansson: oskar.hansson@med.lu.se

Journal

Journal ID (nlm-ta): Acta Neuropathol Commun

Journal ID (iso-abbrev): Acta Neuropathol Commun

Title: Acta Neuropathologica Communications

Publisher: BioMed Central (London )

ISSN (Electronic): 2051-5960

Publication date (Electronic): 6 January 2022

Publication date PMC-release: 6 January 2022

Publication date Collection: 2022

Volume: 10

Electronic Location Identifier: 3

Affiliations

[1 ]GRID grid.4514.4, ISNI 0000 0001 0930 2361, Clinical Memory Research Unit, Department of Clinical Sciences Malmö, , Lund University, ; Inga Marie Nilssons gata 53, 214 28 Malmö, Sweden

[2 ]GRID grid.5640.7, ISNI 0000 0001 2162 9922, Department of Physics, Chemistry and Biology IFM, , Linköping University, ; 581 83 Linköping, Sweden

[3 ]GRID grid.419918.c, ISNI 0000 0001 2171 8263, Netherlands Institute for Neuroscience, ; Meibergdreef 47, 1105 BA Amsterdam, the Netherlands

[4 ]GRID grid.414208.b, ISNI 0000 0004 0619 8759, Banner Sun Health Research Institute, ; Sun City, AZ USA

[5 ]GRID grid.417540.3, ISNI 0000 0000 2220 2544, Eli Lilly and Company, ; Indianapolis, IN USA

[6 ]GRID grid.257413.6, ISNI 0000 0001 2287 3919, Stark Neurosciences Research Institute, , Indiana University School of Medicine, ; Indianapolis, IN USA

[7 ]GRID grid.411843.b, ISNI 0000 0004 0623 9987, Memory Clinic, , Skåne University Hospital, ; Malmö, Sweden

Author information

Malin Wennström http://orcid.org/0000-0002-9957-1801

Article

Publisher ID: 1307

DOI: 10.1186/s40478-021-01307-2

PMC ID: 8734209

PubMed ID: 34991721

SO-VID: c20721f7-0938-457c-889b-cc59de3fc00f

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 22 December 2021

Date accepted : 22 December 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004359, Vetenskapsrådet;

Award ID: 2016-00906

Award ID: 2018-02564

Award Recipient : Malin Wennström Oskar Hansson

Funded by: FundRef http://dx.doi.org/10.13039/501100011898, Marianne and Marcus Wallenberg Foundation;

Award ID: 2015.0125