title: First transgenic rat model developing progressive cortical neurofibrillary tangles.
abstract: Neurofibrillary degeneration induced by misfolded protein tau is considered to be one of the key pathological hallmarks of Alzheimer's disease (AD). In the present study, we have introduced a novel transgenic rat model expressing a human truncated tau that encompasses 3 microtubule binding domains (3R) and a proline-rich region (3R tau151-391). The transgenic rats developed progressive age-dependent neurofibrillary degeneration in the cortical brain areas. Neurofibrillary tangles (NFTs) satisfied several key histological criteria used to identify neurofibrillary degeneration in human Alzheimer's disease including argyrophilia, Congo red birefringence, and Thioflavin S reactivity. Neurofibrillary tangles were also identified with antibodies used to detect pathologic tau in the human brain, including DC11, recognizing an abnormal tau conformation and antibodies that are specific for hyperphosphorylated forms of tau protein. Moreover, neurofibrillary degeneration was characterized by extensive formation of sarkosyl insoluble tau protein complexes consisting of rat endogenous and truncated tau species. Interestingly, the transgenic rats did not show neuronal loss either in the cortex or in the hippocampus. We suggest that novel transgenic rat model for human tauopathy represents a valuable tool in preclinical drug discovery targeting neurofibrillary degeneration of Alzheimer's type.
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, Centre of Excellence for Alzheimer's Disease and Related Disorders, Bratislava, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Filipcik
authors.forename: Norbert
authors.initials: N
authors.lastname: Zilka
authors.forename: Ondrej
authors.initials: O
authors.lastname: Bugos
authors.forename: Juraj
authors.initials: J
authors.lastname: Kucerak
authors.forename: Peter
authors.initials: P
authors.lastname: Koson
authors.forename: Petr
authors.initials: P
authors.lastname: Novak
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic