Cellular localization of p-tau217 in brain and its association with p-tau217 plasma levels
Wennström, Malin LU ; Janelidze, Shorena LU ; Nilsson, K. Peter R. ; Serrano, Geidy E. ; Beach, Thomas G. ; Dage, Jeffrey L. and Hansson, Oskar LU
(2022)
In Acta Neuropathologica Communications
10(1).
- 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... (More)
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.
(Less)
- author
- Wennström, Malin
LU
; Janelidze, Shorena
LU
; Nilsson, K. Peter R.
; Serrano, Geidy E.
; Beach, Thomas G.
; Dage, Jeffrey L.
and Hansson, Oskar
LU
- author collaboration
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, Biomarker, GVB
- in
- Acta Neuropathologica Communications
- volume
- 10
- issue
- 1
- article number
- 3
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:34991721
- scopus:85122739897
- ISSN
- 2051-5960
- DOI
- 10.1186/s40478-021-01307-2
- language
- English
- LU publication?
- yes
- id
- 5fbd16d8-f727-49d0-952a-838f51643d6d
- date added to LUP
- 2022-03-01 11:13:34
- date last changed
- 2024-04-18 06:33:01
@article{5fbd16d8-f727-49d0-952a-838f51643d6d,
abstract = {{<p>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.</p>}},
author = {{Wennström, Malin and Janelidze, Shorena and Nilsson, K. Peter R. and Serrano, Geidy E. and Beach, Thomas G. and Dage, Jeffrey L. and Hansson, Oskar}},
issn = {{2051-5960}},
keywords = {{Alzheimer’s disease; Biomarker; GVB}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Acta Neuropathologica Communications}},
title = {{Cellular localization of p-tau217 in brain and its association with p-tau217 plasma levels}},
url = {{http://dx.doi.org/10.1186/s40478-021-01307-2}},
doi = {{10.1186/s40478-021-01307-2}},
volume = {{10}},
year = {{2022}},
}