Affiliations: [a]
Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic | [b] Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic | [c] Axon Neuroscience SE, Bratislava, Slovak Republic
Correspondence:
[*]
Correspondence to: Norbert Zilka, Axon Neuroscience R&D Services SE, Dvorakovo nabrezie 10, 811 02 Bratislava, Slovak Republic. Tel.: +421 907 756 744; E-mail: [email protected].
Abstract: Alzheimer’s disease (AD) represents the most common neurodegenerative disorder. Several animal models have been developed in order to test pathophysiological mechanisms of the disease and to predict effects of pharmacological interventions. Here we examine the molecular and behavioral features of R3m/4 transgenic mice expressing human non-mutated truncated tau protein (3R tau, aa151–391) that were previously used for efficacy testing of passive tau vaccine. The mouse model reliably recapitulated crucial histopathological features of human AD, such as pre-tangles, neurofibrillary tangles, and neuropil threads. The pathology was predominantly located in the brain stem. Transgenic mice developed mature sarkosyl insoluble tau complexes consisting of mouse endogenous and human truncated and hyperphosphorylated forms of tau protein. The histopathological and biochemical features were accompanied by significant sensorimotor impairment and reduced lifespan. The sensorimotor impairment was monitored by a highly sensitive, fully-automated tool that allowed us to assess early deficit in gait and locomotion. We suggest that the novel transgenic mouse model can serve as a valuable tool for analysis of the therapeutic efficacy of tau vaccines for AD therapy.
Keywords: Alzheimer’s disease, neurofibrillary degeneration, tauopathies, transgenic mouse, truncated tau protein
