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

• Published in: Acta neuropathologica communications Vol. 10; no. 1; pp. 3 - 12
• Main Authors: Wennström, Malin, Janelidze, Shorena, Nilsson, K. Peter R., Serrano, Geidy E., Beach, Thomas G., Dage, Jeffrey L., Hansson, Oskar
• Format: Journal Article
• Language: English
• Published: London BioMed Central 06.01.2022; BioMed Central Ltd; BMC
• Subjects: Advertising executives; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Antibodies; Basic Medicine; Biomarker; Biomarkers; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Brain - pathology; Brain research; Ethylenediaminetetraacetic acid; Female; GVB; Humans; Ligands; Localization; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurology; Neurons - metabolism; Neurons - pathology; Neuropathology; Neurosciences; Neurovetenskaper; Pathology; Phosphorylation; Physiological aspects; Plasma; tau Proteins - blood; tau Proteins - metabolism; Tauopathies - blood; Tauopathies - metabolism; Tauopathies - pathology; Alzheimer’s disease; Biomarker; GVB; Alzheimers disease
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-021-01307-2

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.