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Publication : Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy.

First Author  Patel H Year  2022
Journal  Neurobiol Aging Volume  109
Pages  52-63 PubMed ID  34655981
Mgi Jnum  J:355359 Mgi Id  MGI:6854595
Doi  10.1016/j.neurobiolaging.2021.09.006 Citation  Patel H, et al. (2022) Pathological tau and reactive astrogliosis are associated with distinct functional deficits in a mouse model of tauopathy. Neurobiol Aging 109:52-63
abstractText  Pathological aggregation of tau and neuroinflammatory changes mark the clinical course of Alzheimer's disease and related tauopathies. To understand the correlation between these pathological hallmarks and functional deficits, we assessed behavioral and physiological deficits in the PS19 mouse model, a broadly utilized model of tauopathy. At 9 months, PS19 mice have characteristic hyperactive behavior, a decline in motor strength, and deterioration in physiological conditions marked by lower body temperature, reduced body weight, and an increase in measures of frailty. Correlation of these deficits with different pathological hallmarks revealed that pathological tau species, characterized by soluble p-tau species, and tau seeding bioactivity correlated with impairment in grip strength and thermal regulation. On the other hand, astrocyte reactivity showed a positive correlation with the hyperactive behavior of the PS19 mice. These results suggest that a diverse spectrum of soluble pathological tau species could be responsible for different symptoms and that neuroinflammation could contribute to functional deficits independently from tau pathology. These observations enhance the necessity of a multi-targeted approach for the treatment of neurodegenerative tauopathies.
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