Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 50, Pages E8187-E8196Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1616344113
Keywords
argyrophilic grain disease; corticobasal degeneration; Pick's disease; progressive supranuclear palsy; tauopathies
Categories
Funding
- NIH [AG002132, AG031220, AG023501, AG19724]
- Daiichi Sankyo
- Dana Foundation
- Glenn Foundation
- Sherman Fairchild Foundation
- Tau Consortium
- Consortium for Frontotemporal Dementia Research
- Department of Veterans Affairs, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering [NS086559]
- National Institute on Aging, Boston University Alzheimer's Disease Center [AG13846, 0572063345-5]
- Concussion Legacy Foundation
- Andlinger Foundation
- World Wrestling Entertainment, Inc
Ask authors/readers for more resources
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 HEK293T 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available