Neuronal activity enhances tau propagation and tau pathology in vivo.
Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau pathology in vivo. These data have implications for disease pathogenesis and therapeutic strategies for Alzheimer's disease and other tauopathies.
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Jessica W
JW
Wu
Taub Institute, Columbia University Medical Center, New York, New York, USA.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
S Abid
SA
Hussaini
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Isle M
IM
Bastille
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Gustavo A
GA
Rodriguez
Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Ana
A
Mrejeru
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Kelly
K
Rilett
Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
David W
DW
Sanders
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Casey
C
Cook
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Hongjun
H
Fu
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Rick A C M
RA
Boonen
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Mathieu
M
Herman
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Eden
E
Nahmani
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Sheina
S
Emrani
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Y Helen
YH
Figueroa
Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Marc I
MI
Diamond
Taub Institute, Columbia University Medical Center, New York, New York, USA.
Catherine L
CL
Clelland
Department of Molecular Neuroscience, Institute of Neurology, University College, London, UK.
Selina
S
Wray
Taub Institute, Columbia University Medical Center, New York, New York, USA.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.|Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York, USA.
Karen E
KE
Duff
D000818:Animals; D001921:Brain / Q000378:metabolism*; D008822:Mice, Transgenic; D013569:Synapses / Q000378:metabolism*; D024801:Tauopathies / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins