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P2‐162: TARG1 promotes PHF‐positive phosphorylation and aggregation of tau in vitro and in vivo
Author(s) -
Park Hyejin,
Choi Hyunwoo,
Kim Young Doo,
Kim Hyung-jun,
Kim Changsoo,
Jung Yong-Keun
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1236
Subject(s) - tauopathy , neurodegeneration , phosphorylation , hyperphosphorylation , microbiology and biotechnology , tau protein , biology , ectopic expression , phenotype , cyclin dependent kinase 5 , chemistry , neuroscience , alzheimer's disease , gene , biochemistry , medicine , pathology , protein kinase a , mitogen activated protein kinase kinase , disease
and PHF-1, phosphorylation-dependent antibodies. We performed a cell count analysis with NeuN (neuron specific nuclear protein) antibody in the parahippocampal area. We also evaluated the immunoreactivity of PSD95 (postsynaptic density) as a postsynaptic marker. Results: The levels of exogenous tau expression of Wtau-Tg was fourto eightfold higher than those of endogenous tau. TBS-soluble tau was expressed in all cortical regions, the hippocampus, caudate, putamen and thalamus but not in the spinal cord. Numerous AT8-positive neurons were observed in the hippocampus and neocortex at 4 months. There was neither Gallyas-positive nor Thioflavin-S positive neurons at 24 months. The western blot findings by AT8, AT180 and PHF-1 showed tau in the TBS soluble fractions was phosphorylated at 4 months. The levels of phosphorylation of tau increased with age. The sarcosyl-insolble fraction did not display positive tau signals. For EPM, Wtau-Tg spent more time in the open arms at 14 months but not 4 months. For the MWM test, Wtau-Tg showed impaired place learning ability at 14 months but not 4 months. Conclusions: The accumulation of phosphoryated tau that occurs before NFT formation may contribute to impaired learning and behavioral abnormality in Alzheimer’s disease.