Neuronal activity enhances tau propagation and tau pathology in vivo
Open accessAbstract
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.
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Both Aβ and tau are released with normal network activity, so each protein most likely serves a physiological purpose.
“Both A and tau are released with normal network activity, so each protein most likely serves a physiological purpose (51,52).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [52]
Increased neuronal activity enhances the release of tau-containing exosomes and exacerbates tau propagation and pathology.
“Increased neuronal activity enhances the release of tau-containing exosomes [75] and exacerbates tau propagation and pathology [78].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [78]
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“DISCUSSION Using a variety of in vitro cell models, we have shown that (1) neuronderived full-length tau can transfer to recipients and aggregated tau can be induced by seeding transfers efficiently, (2) neuronderived tau can not only be internalized by recipient neurons but can also undergo transcellular propagation…”
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“Both A and tau are released with normal network activity, so each protein most likely serves a physiological purpose (51, 52).”
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Self-citation
- Authors
- Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A. C. M., Herman, M., Nahmani, E., Emrani, S., Figueroa, Y. H., Diamond, M. I., Clelland, C. L., Wray, S., & Duff, K. E.
- Affiliations
- Columbia University Irving Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Mayo Clinic (US)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Duff, Karen E
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2016-08
- Volume
- 19
- Issue
- 8
- Pages
- 1085-1092
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4961585
- OpenAlex
- W2472346278
- Cited by
- 820
- References
- 51
- Citations by year
- 2026: 61 · 2025: 88 · 2024: 112 · 2023: 88 · 2022: 93 · 2021: 96 · 2020: 84 · 2019: 65 · 2018: 65 · 2017: 58 · 2016: 10
- FWCI
- 53.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA019801)
- National Institute on Aging (R01AG050425)
- National Institute of General Medical Sciences (T32GM008151)
- National Institute of Neurological Disorders and Stroke (R01NS074874, R01NS081555)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tau protein, tauopathy, Alzheimer's disease, neuronal activity, tau pathology, optogenetics, chemogenetics, tau secretion, pathogenesis
- MeSH terms
- Animals, Brain, Mice, Transgenic, Synapses, tau Proteins, Tauopathies
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