TitleTau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsWoerman AL, Aoyagi A, Patel S, Kazmi SA, Lobach I, Grinberg LT, McKee AC, Seeley WW, Olson SH, Prusiner SB
JournalProc Natl Acad Sci U S A
Date Published2016 12 13
KeywordsAlzheimer Disease, Bacterial Proteins, Cell Line, Chronic Traumatic Encephalopathy, HEK293 Cells, Humans, Luminescent Proteins, Mutation, Pick Disease of the Brain, Protein Isoforms, Recombinant Fusion Proteins, Supranuclear Palsy, Progressive, tau Proteins, Up-Regulation

Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from AGD, CBD, and PSP patient samples, which contain four-repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R isoforms, were unable to robustly infect either 3R- or 4R-expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27911827
PubMed Central IDPMC5167200
Grant ListP50 AG023501 / AG / NIA NIH HHS / United States
P01 AG002132 / AG / NIA NIH HHS / United States
R37 AG031220 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States