Abnormal processing of tau in the brain of aged TgCRND8 mice.
Amyloid plaques and neurofibrillary tangles are the main histopathological hallmarks of Alzheimer's disease (AD). In the neocortex and hippocampus of aged TgCRND8 mice, tau is hyperphosphorylated at different sites recognized by PHF-1, AT100, AT8 and CP13 antibodies. Phospho-SAPK/JNK levels were increased in the tg mouse brain, where activated SAPK/JNK co-localizes with PHF-1-positive cells. Phosphorylated tau-positive cells showed Bielschowsky- and Thioflavine S-positive intraneuronal deposits. PHF-1 and nitrotyrosine immunoreactivity merged within neurons surrounding amyloid deposits in cortical and hippocampal areas and immunoprecipitation studies confirmed that tau is nitrosylated. Our findings, demonstrating the presence of hyperphosphorylated and nitrosylated tau protein as well as of insoluble aggregates after the onset of amyloid deposition in the TgCRND8 mouse brain, indicate that the abnormal processing of tau may occur subsequently to cerebral amyloidosis and that activation of SAPK/JNK and induction of nitrosative stress are the more likely connecting factors between amyloidosis and tauopathy in AD.
Bellucci
Arianna
A
Biomedical Sciences and Biotechnology, Division of Pharmacology, University of Brescia, Viale Europa, 11, 25123, Italy.
Rosi
Maria Cristina
MC
Grossi
Cristina
C
Fiorentini
Anna
A
Luccarini
Ilaria
I
Casamenti
Fiorella
F
D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D048670:MAP Kinase Kinase 4