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Transmission of tauopathy strains is independent of their isoform composition

Author

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  • Zhuohao He

    (University of Pennsylvania School of Medicine
    Chinese Academy of Sciences)

  • Jennifer D. McBride

    (University of Pennsylvania School of Medicine)

  • Hong Xu

    (University of Pennsylvania School of Medicine)

  • Lakshmi Changolkar

    (University of Pennsylvania School of Medicine)

  • Soo-jung Kim

    (University of Pennsylvania School of Medicine)

  • Bin Zhang

    (University of Pennsylvania School of Medicine)

  • Sneha Narasimhan

    (University of Pennsylvania School of Medicine)

  • Garrett S. Gibbons

    (University of Pennsylvania School of Medicine)

  • Jing L. Guo

    (University of Pennsylvania School of Medicine)

  • Michael Kozak

    (University of Pennsylvania School of Medicine)

  • Gerard D. Schellenberg

    (University of Pennsylvania School of Medicine)

  • John Q. Trojanowski

    (University of Pennsylvania School of Medicine)

  • Virginia M. -Y. Lee

    (University of Pennsylvania School of Medicine)

Abstract

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.

Suggested Citation

  • Zhuohao He & Jennifer D. McBride & Hong Xu & Lakshmi Changolkar & Soo-jung Kim & Bin Zhang & Sneha Narasimhan & Garrett S. Gibbons & Jing L. Guo & Michael Kozak & Gerard D. Schellenberg & John Q. Troj, 2020. "Transmission of tauopathy strains is independent of their isoform composition," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13787-x
    DOI: 10.1038/s41467-019-13787-x
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    Cited by:

    1. Alexa Pichet Binette & Nicolai Franzmeier & Nicola Spotorno & Michael Ewers & Matthias Brendel & Davina Biel & Olof Strandberg & Shorena Janelidze & Sebastian Palmqvist & Niklas Mattsson-Carlgren & Ru, 2022. "Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Nicolai Franzmeier & Matthias Brendel & Leonie Beyer & Luna Slemann & Gabor G. Kovacs & Thomas Arzberger & Carolin Kurz & Gesine Respondek & Milica J. Lukic & Davina Biel & Anna Rubinski & Lukas Front, 2022. "Tau deposition patterns are associated with functional connectivity in primary tauopathies," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Satra Nim & Darren M. O’Hara & Carles Corbi-Verge & Albert Perez-Riba & Kazuko Fujisawa & Minesh Kapadia & Hien Chau & Federica Albanese & Grishma Pawar & Mitchell L. Snoo & Sophie G. Ngana & Jisun Ki, 2023. "Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Aurelio J. Dregni & Pu Duan & Hong Xu & Lakshmi Changolkar & Nadia El Mammeri & Virginia M.-Y. Lee & Mei Hong, 2022. "Fluent molecular mixing of Tau isoforms in Alzheimer’s disease neurofibrillary tangles," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Sukanta Jash & Sayani Banerjee & Shibin Cheng & Bin Wang & Chenxi Qiu & Asami Kondo & Jan Ernerudh & Xiao Zhen Zhou & Kun Ping Lu & Surendra Sharma, 2023. "Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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