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Insoluble Tau From Human FTDP-17 Cases Exhibit Unique Transmission Properties In Vivo.

TitleInsoluble Tau From Human FTDP-17 Cases Exhibit Unique Transmission Properties In Vivo.
Publication TypeJournal Article
Year of Publication2020
AuthorsWeitzman SA, Narasimhan S, He Z, Changolkar L, McBride JD, Zhang B, Schellenberg GD, Trojanowski JQ, M Y Lee V
JournalJ Neuropathol Exp Neurol
Date Published2020 09 01
KeywordsAnimals, Female, Frontotemporal Dementia, Humans, Male, Mice, Mice, Inbred C57BL, tau Proteins

One hallmark of neurodegenerative diseases is the intracellular accumulation of hyperphosphorylated tau protein, a neuronal microtubule-associated protein, into structures known as neurofibrillary tangles. Tauopathies are heterogeneous neurodegenerative diseases caused by the misfolding of the tau protein. It has been previously shown that the tau protein can spread from cell to cell in a prion-like manner. Tauopathies can be sporadic or familial, with the identification of pathogenic mutations in the microtubule-associated protein tau gene on chromosome 17 in the familial cases. Different frontotemporal dementia with parkinsonism-17 (FTDP-17) cases are associated with varying clinical presentations and types of neuropathology. We previously demonstrated that insoluble tau extracted from sporadic tauopathy human brains contain distinct tau strains, which underlie the heterogeneity of these diseases. Furthermore, these tau strains seeded tau aggregates that resemble human tau neuropathology in nontransgenic and 6hTau mice in vivo. Here, we show insoluble tau from human brains of FTDP-17 cases transmit different patterns of neuronal and glial tau pathology in vivo, similar to the sporadic tauopathies. This suggests that each of these tau mutations has unique properties that underlie the heterogeneity of FTDP-17 cases.

Pubmed Link
Alternate JournalJ Neuropathol Exp Neurol
PubMed ID32838419
PubMed Central IDPMC7445034
Grant ListP01 AG017586 / AG / NIA NIH HHS / United States
U19 AG062418 / AG / NIA NIH HHS / United States

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