Tau protein is hyperphosphorylated in the brain of 7-month-old TgCRND8 mice

FENS Forum 2006 First author: Casamenti, Fiorella (poster) Poster board 443 - Mon 10/07, 12:15 - Hall Y Session 092 - Alzheimer's disease I Abstract A092.6, published in FENS Forum Abstracts, vol. 3, 2006. Ref.: FENS Abstr., vol.3, A092.6, 2006 Author(s) Casamenti F. (1), Bellucci A. (2), Rosi M. C. (1), Grossi C. (1), Luccarini I. (1), Fiorentini A. (1) & Pepeu G. (1) Addresse(s) (1) Dept. Pharmacol., Univ. Florence, Florence, Italy; (2) Dept. Pharmacol., Univ. Brescia, Brescia, Italy Title Tau protein is hyperphosphorylated in the brain of 7-month-old TgCRND8 transgenic mice. Text Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized pathologically by the presence of senile plaques, neurofibrillary tangles and marked neuronal death in the brain of affected patients. Several lines of transgenic mice have been created to investigate the underlying neurodegenerative mechanisms in AD and to test new therapeutic approaches. Transgenic TgCRND8 mice (Chishti et al., 2001, J. Biol. Chem. 276, 21562) expressing a double mutant form of amyloid precursor protein (APP) have been produced. In 7-month-old TgCRND8 mice the presence of tau hyperphosphorylation and tyrosine-nitrosylation was verified and the link between amyloid deposits, inflammatory reaction and tau tangles and their contribution to neuronal death was investigated. Clusters of activated microglia and astrocytes, iNOS-positive microglia and neurons were found in the surrounding of plaques. Numerous hyperphosphorylated tau- immunopositive neurons were detected in the cortex and hippocampus of TgCRND8 mouse brain and some of the tau-5 positive neurons surrounding the amyloid plaques were also PHF-1 positive. These neurons were also positive for thioflavin-S and Bielshowsky staining, thus indicating a fibrillary state of tau. Western blot analysis revealed that the tau band was AT-8 and AT-100 immunopositive. In the cortex and CA1, CA3 and dentate gyrus of hippocampus, PHF-1 immunoreactivity co-localized with nitrotyrosine staining, suggesting a role for tyrosine nitrosylation in tau conformational changes. PHF-1 and nitrotyrosine staining was localized in the cytoplasm and in neuropile threads. Moreover, in the transgenic mouse brain, SAPK/JNK activation was increased compared to wt mice. These findings demonstrate that amyloid deposition and the associated neuroinflammation trigger a series of events leading to tau hyperphosphorylation and deposition. Supported by Ente CRF and PRIN/MIUR 2005. We thank Dr. S Hyslop for kindly supplying the TgCRND8 mice. Theme Neurological and psychiatric conditions Neurodegenerative disorders / Alzheimers disease: Tau