Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo

Sílvia Porta; Yan Xu; Clark R. Restrepo; Linda K. Kwong; Bin Zhang; Hannah J. Brown; Edward B. Lee; John Q. Trojanowski; Virginia M.-Y. Lee

doi:10.1038/s41467-018-06548-9

Nature Communications (Oct 2018)

Patient-derived frontotemporal lobar degeneration brain extracts induce formation and spreading of TDP-43 pathology in vivo

Sílvia Porta,
Yan Xu,
Clark R. Restrepo,
Linda K. Kwong,
Bin Zhang,
Hannah J. Brown,
Edward B. Lee,
John Q. Trojanowski,
Virginia M.-Y. Lee

Affiliations

Sílvia Porta: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Yan Xu: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Clark R. Restrepo: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Linda K. Kwong: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Bin Zhang: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Hannah J. Brown: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Edward B. Lee: Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
John Q. Trojanowski: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
Virginia M.-Y. Lee: Center for Neurodegenerative Disease Research (CNDR), Institute on Aging, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

DOI: https://doi.org/10.1038/s41467-018-06548-9
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 15

Abstract

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Cell-to-cell transmission of TDP43 occurs in cell cultures and may contribute to pathological TDP43 propagation in FTLD-TDP. In this study, the authors demonstrate using mouse models that a single intracerebral injection of human brain-derived pathological TDP43 from FTLD-TDP cases initiates the process of seeding and spreading of TDP43 pathology in a spatio-temporal dependent manner in the brain.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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