α-Synuclein modulates tau spreading in mouse brains
| Autor: | Bin Zhang, Virginia M.-Y. Lee, Chantal M. Maghames, Timothy O. Cox, Qihui Wu, Shankar Pattabhiraman, Hong Xu, Fares Bassil, John Q. Trojanowski, Hannah J. Brown, Emily S. Meymand |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Tau pathology animal diseases Immunology tau Proteins Endogeny Fibril Article Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease In vivo mental disorders Animals Immunology and Allergy heterocyclic compounds In patient Mice Knockout Chemistry Brain Parkinson Disease In vitro nervous system diseases Cell biology Crosstalk (biology) 030104 developmental biology nervous system health occupations alpha-Synuclein α synuclein 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Bassil et al. model the crosstalk of α-syn and tau under copathology conditions. They show evidence of α-syn–dependent tau pathology in the human brain. Moreover, they demonstrate the role of α-syn in the modulation of tau pathology in mice. α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson’s disease (PD) and Alzheimer’s disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate–derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients. |
| Databáze: | OpenAIRE |
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