Tauopathies are characterized by abnormal accumulation of tau protein in neurons and glia. In Alzheimer’s disease (AD), tau aggregates in neurons, while in corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), tau also aggregates in astrocytes and oligodendrocytes. We previously demonstrated that human CBD and PSP tauopathy lysates (CBD-tau and PSP-tau) contain distinct tau strains that propagate neuronal and glial tau aggregates in nontransgenic (nonTg) mouse brain. Yet the mechanism of glial tau transmission is unknown. Here, we developed a novel mouse model to knock down tau in neurons to test for glial tau transmission. While oligodendroglial tau pathology propagated across the mouse brain in the absence of neuronal tau pathology, astrocytic tau pathology did not. Oligodendroglial tau aggregates propagated along white matter tracts independently of neuronal axons, and resulted in oligodendrocyte cell loss. Thus, glial tau pathology has significant functional consequences independent of neuronal tau pathology.
Human tau pathology transmits glial tau aggregates in the absence of neuronal tau
- Views Icon Views
- Share Icon Share
- Tools Icon Tools
- Search Site
Sneha Narasimhan, Lakshmi Changolkar, Dawn M. Riddle, Alexandra Kats, Anna Stieber, Sarah A. Weitzman, Bin Zhang, Zhiyong Li, Erik D. Roberson, John Q. Trojanowski, Virginia M.Y. Lee; Human tau pathology transmits glial tau aggregates in the absence of neuronal tau. J Exp Med 3 February 2020; 217 (2): e20190783. doi: https://doi.org/10.1084/jem.20190783
Download citation file: