Tau propagation is dependent on the genetic background of mouse strains
Open accessAbstract
Progressive cognitive decline in Alzheimer’s disease correlates closely with the spread of tau protein aggregation across neural networks of the cortical mantle. We tested the hypothesis that heritable factors may influence the rate of propagation of tau pathology across brain regions in a model system, taking advantage of well-defined genetically diverse background strains in mice. We virally expressed human tau locally in the hippocampus and the entorhinal cortex neurons and monitored the cell-to-cell tau protein spread by immunolabelling. Interestingly, some strains showed more tau spreading than others while tau misfolding accumulated at the same rate in all tested mouse strains. Genetic factors may contribute to tau pathology progression across brain networks, which could help refine mechanisms underlying tau cell-to-cell transfer and accumulation, and potentially provide targets for understanding patient-to-patient variability in the rate of disease progression in Alzheimer’s disease.
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Recent studies in AD have shown that mouse genetic background can modulate Aβ accumulation, immune response, and tau propagation.
“Recent studies in AD have shown that mouse genetic background can modulate Aβ accumulation (Onos et al., 2019), immune response (Yang et al., 2021), and tau propagation (Dujardin et al., 2022).”
From Network analysis identifies strain-dependent response to tau and tau seeding-associated genes (2023) · cites this paper as Dujardin et al., 2022
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Murakami, R., Watanabe, H., Hashimoto, H., Kashiwagi-Hakozaki, M., Hashimoto, T., Karch, C. M., the Dominantly Inherited Alzheimer Network (DIAN), Iwatsubo, T., & Okano, H. (2024) · The Journal of Neuroscience · doi:10.1523/jneurosci.1709-23.2024 · Cited by 9 · see citing works
Network analysis identifies strain-dependent response to tau and tau seeding-associated genes
Acri, D. J., You, Y., Tate, M. D., Karahan, H., Martinez, P., McCord, B., Sharify, A. D., John, S., Kim, B., Dabin, L. C., et al. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20230180 · Cited by 3 · see citing works
“…et al., 2016; Cook et al., 2014), neuro-inflammation (Yoshiyama et al., 2007), prion-like proteopathic seeding (Martinez et al., 2022), and propagation from one cell to another (Dujardin et al., 2022; Rauch et al., 2020; Wegmann et al., 2017; de Calignon et al., 2012; Woerman et al., 2017).”
- Authors
- Dujardin, S., Fernandes, A., Bannon, R., Commins, C., De Los Santos, M., Kamath, T. V., Hayashi, M., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA
- Eli Lilly (United States) (US)
- Corresponding author
- Hyman, Bradley T.
- Venue
- Brain Communications
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-02-23
- Volume
- 4
- Issue
- 2
- Pages
- fcac048-fcac048
- ISSN
- 2632-1297 (ISSN-L)
- PMC
- PMC8952249
- OpenAlex
- W4213199509
- Cited by
- 11
- References
- 8
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 4 · 2022: 1
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- Eli Lilly and Company
- Rainwater Foundation
- JPB Foundation
- Alzheimer’s Association (2018-AARF-591935)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau propagation, Alzheimer's disease, genetic background, mouse strains, tau misfolding, hippocampus, entorhinal cortex, genetic diversity
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