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Transmission of tauopathy strains is independent of their isoform composition.

TitleTransmission of tauopathy strains is independent of their isoform composition.
Publication TypeJournal Article
Year of Publication2020
AuthorsHe Z, McBride JD, Xu H, Changolkar L, Kim S-J, Zhang B, Narasimhan S, Gibbons GS, Guo JL, Kozak M, Schellenberg GD, Trojanowski JQ, Lee VM-Y
JournalNat Commun
Date Published2020 01 07
KeywordsAnimals, Brain, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Protein Isoforms, tau Proteins, Tauopathies

The deposition of pathological tau is a common feature in several neurodegenerative tauopathies. Although equal ratios of tau isoforms with 3 (3R) and 4 (4R) microtubule-binding repeats are expressed in the adult human brain, the pathological tau from different tauopathies have distinct isoform compositions and cell type specificities. The underlying mechanisms of tauopathies are unknown, partially due to the lack of proper models. Here, we generate a new transgenic mouse line expressing equal ratios of 3R and 4R human tau isoforms (6hTau mice). Intracerebral injections of distinct human tauopathy brain-derived tau strains into 6hTau mice recapitulate the deposition of pathological tau with distinct tau isoform compositions and cell type specificities as in human tauopathies. Moreover, through in vivo propagation of these tau strains among different mouse lines, we demonstrate that the transmission of distinct tau strains is independent of strain isoform compositions, but instead intrinsic to unique pathological conformations.

Pubmed Link
Alternate JournalNat Commun
PubMed ID31911587
PubMed Central IDPMC6946697
Grant ListP30 AG010124 / AG / NIA NIH HHS / United States
P01 AG017586 / AG / NIA NIH HHS / United States
U19 AG062418 / AG / NIA NIH HHS / United States
U54 NS100693 / NS / NINDS NIH HHS / United States

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