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

Autor: Malin Wennström, Shorena Janelidze, K. Peter R. Nilsson, The Netherlands Brain Bank, Geidy E. Serrano, Thomas G. Beach, Jeffrey L. Dage, Oskar Hansson
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 10, Iss 1, Pp 1-12 (2022)
Druh dokumentu: article
ISSN: 2051-5960
DOI: 10.1186/s40478-021-01307-2
Popis: 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.
Databáze: Directory of Open Access Journals
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