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Cited by 59Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Wennström, Malin, Janelidze, Shorena, Nilsson, K. Peter R., The Netherlands Brain Bank, Serrano, Geidy E., Beach, Thomas G., Dage, Jeffrey L., Hansson, Oskar·2022·Acta Neuropathologica Communications
DOI 10.1186/s40478-021-01307-2PMC PMC8734209
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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.

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References 30 · Cited by 59

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Authors
Wennström, M., Janelidze, S., Nilsson, K. P. R., Bank, T. N. B., Serrano, G. E., Beach, T. G., Dage, J. L., & Hansson, O.
Affiliations
  • Lund University (SE)
  • Linköping University (SE)
  • Netherlands Institute for Neuroscience (NL)
  • Banner Sun Health Research Institute (US)
  • Eli Lilly (United States) (US)
Corresponding author
  • Wennström, Malin
  • Hansson, Oskar
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2022-01-06
Volume
10
Issue
1
Pages
3-3
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-021-01307-2
PMC
PMC8734209
OpenAlex
W4206731714
Cited by
59
References
30
Citations by year
2026: 7 · 2025: 10 · 2024: 13 · 2023: 12 · 2022: 17
FWCI
8.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • DiVA (Linkoping University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Vetenskapsrådet (2016-00906, 2018-02564)
  • Marianne and Marcus Wallenberg Foundation (2015.0125)
  • Multidisciplinary Research in Parkinson’s disease
  • Swedish Alzheimer Foundation (AF-939932)
  • Hjärnfonden (FO2021-0293)
  • The Parkinson foundation of Sweden (1280/20)
  • the Skåne University Hospital Foundation (2020-O000028)
  • Regionalt Forskningsstöd (2020-0314)
  • the Swedish federal government under the ALF agreement (2018-Projekt0279)
  • the National Institute of Neurological Disorders and Stroke (U24 NS072026)
  • National Institute on Aging (P30 AG19610)
  • Arizona Department of Health Services (211002)
  • Arizona Biomedical Research Commission (4001, 0011, 05-901, 1001)
  • Michael J. Fox Foundation for Parkinson's Research
  • LRAP
  • Lund University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
phosphorylated tau, Alzheimer's disease, plasma biomarkers, neurofibrillary tangles, neuropil threads, granulovacuolar degeneration, multivesicular bodies, amyloid plaques, primary age-related tauopathy, postmortem neuropathology, entorhinal cortex, inferior temporal gyrus, superior frontal gyrus
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Middle Aged, Neurons, Phosphorylation, Neurofibrillary Tangles, tau Proteins, Tauopathies

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