Limitations and Applications of Rodent Models in Tauopathy and Synucleinopathy Research

Rodent models that accurately recapitulate key aspects of human disease have long been fundamental to the successful development of clinical interventions. This is greatly underscored in the neurodegenerative disease field, where preclinical testing of anti-prion therapeutics against rodent-adapted prions resulted in the development of small molecules effective against rodent-adapted prions but not against human prions. These findings provided critical lessons for ongoing efforts to develop treatments for patients with neurodegenerative diseases caused by misfolding and accumulation of the proteins tau and α-synuclein, or tauopathies and synucleinopathies, respectively. To avoid the potential pitfalls previously identified in the prion field, this review focuses on rodent models currently available to study tau and α-synuclein disease pathogenesis, emphasizing the strengths and limitations of each with the particular goal of better supporting preclinical research.