title: Human Truncated Tau Induces Mature Neurofibrillary Pathology in a Mouse Model of Human Tauopathy.
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.
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Ivana
authors: I
authors: Zimova
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.
authors: Veronika
authors: V
authors: Brezovakova
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Tomas
authors: T
authors: Hromadka
authors: Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Petronela
authors: P
authors: Weisova
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Veronika
authors: V
authors: Cubinkova
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Bernadeta
authors: B
authors: Valachova
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Peter
authors: P
authors: Filipcik
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.
authors: Santosh
authors: S
authors: Jadhav
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Tomas
authors: T
authors: Smolek
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience SE, Bratislava, Slovak Republic.
authors: Michal
authors: M
authors: Novak
authors: Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.|Axon Neuroscience R&D Services SE, Bratislava, Slovak Republic.
authors: Norbert
authors: N
authors: Zilka
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000096:biosynthesis*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer’s disease; neurofibrillary degeneration; tauopathies; transgenic mouse; truncated tau protein