caa a22 4500 467881901 CHVBK 20180406152722.0 cr unu---uuuuu 170328e20061101xx s 000 0 eng 10.1007/s00702-006-0507-5 doi (NATIONALLICENCE)springer-10.1007/s00702-006-0507-5 Endogenous overproduction of β-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells [Elektronische Daten] [Y.-P. Wang, X.-C. Wang, Q. Tian, Y. Yang, Q. Zhang, J.-Y. Zhang, Y.-C. Zhang, Z.-F. Wang, Q. Wang, H. Li, J.-Z. Wang] Summary.: Although neurofibrillary tangles and senile plaques have been identified as the hallmark pathological changes in the brain of Alzheimer's disease (AD), the relationship between them is still not fully understood. In the present study, we have studied the effect of endogenously overproduced amyloid β (Aβ) on tau by using wild type amyloid precursor protein (APP) transfected (N2a/APP695), or Swedish mutant APP plus Δ9 deleted presenilin-1 co-transfected (N2a/APPswe.Δ9) and APP vector transfected (N2a/vector) cell lines. We measured the secreted and intracellular Aβ, including Aβ1-40 and Aβ1-42, by Sandwich ELISA assay. It was shown that the levels of Aβ were increased time-dependently in N2a/APP695 and N2a/APPswe.Δ9 but not in N2a/vector upon butyric acid (BA) treatment. Compared with N2a/vector cells, tau in N2a/APP695 and N2a/APPswe.Δ9 cells was not extracted by RIPA buffer, and the SDS-extracted tau protein was hyperphosphorylated at Tau-1 and PHF-1 epitopes upon BA treatment. Obvious accumulation of the hyperphosphorylated tau in N2a/APP695 and N2a/APPswe.Δ9 cells was observed at 48 h after BA treatment. The total level of the extracted tau was reduced in N2a/APP695 and N2a/APPswe.Δ9 lines compared with N2a/vector cells by Western blot, and this reduction of total tau was also detected by immunofluorescence staining. No obvious alteration of tau mRNA was observed in both N2a/APP695 and N2a/APPswe.Δ9 cells compared with N2a/vector. This study provides direct evidence demonstrating that endogenously overproduced Aβ not only induces tau hyperphosphorylation but also decreases the level and solubility of tau in N2a cell lines. Springer-Verlag, 2006 Keywords: Alzheimer's disease, β-amyloid, tau nationallicence AD : Alzheimer's disease nationallicence FAD : familial Alzheimer disease nationallicence Aβ : β amyloid nationallicence APP : amyloid precursor protein nationallicence PS : presenilin nationallicence BA : butyric acid nationallicence SP : senile plaque nationallicence NFT : neurofibrillary tangle nationallicence BCIP/NBT : 5-bromo-4-chloro-3-indolyl-phosphate/nitroblue tetrazolium nationallicence ELISA : enzyme linked immunosorbent assay nationallicence Wang Y.-P Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Wang X.-C Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Tian Q. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Yang Y. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Zhang Q. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Zhang J.-Y Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Zhang Y.-C Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Wang Z.-F Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Wang Q. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Li H. Hubei Provincial Key Laboratory in Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technical, Wuhan, China aut Wang J.-Z Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut Journal of Neural Transmission Springer-Verlag 113/11(2006-11-01), 1723-1732 0300-9564 113:11<1723 2006 113 702 https://doi.org/10.1007/s00702-006-0507-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-006-0507-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Y.-P Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Wang X.-C Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Tian Q. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Yang Y. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Zhang Q. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Zhang J.-Y Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Zhang Y.-C Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Wang Z.-F Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Wang Q. Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Li H. Hubei Provincial Key Laboratory in Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 700 1- Wang J.-Z Pathophysiology Department, Huazhong University of Science and Technical, Wuhan, China aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer-Verlag 113/11(2006-11-01), 1723-1732 0300-9564 113:11<1723 2006 113 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer