@article{6698699649e8418e869fd32981df7ef8,
title = "Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice",
abstract = "Alzheimer's disease (AD) in the elderly is frequently accompanied by chronic cerebral hypoperfusion (CCH), which impairs the clearance of amyloid beta (Aβ) due to the dysfunction of the blood–brain barrier (BBB) and accelerates the AD pathology. Since the coagulation and complement cascades are associated with BBB dysfunction and AD pathology, we investigated the expression changes of coagulation (fibrinogen alpha chain-FGA, coagulation factor XIII A chain-Factor XIIIα) and complement (plasma protease C1 inhibitor-C1-INH, Complement component 3-C3) factors in the brain of novel AD model (APP23) mice with CCH at 12 months of age. Immunohistochemical and immunofluorescent analysis showed that the expressions of FGA, Factor XIIIα, C1-INH and C3 were significantly increased in cerebral neocortex, hippocampus, and thalamus of APP23 + CCH group (n = 12) as compared with wild type (WT, n = 10) and APP23 (n = 10) groups (⁎P < .05 and ⁎⁎P < .01 vs WT; #P < .05 and ##P < .01 vs APP23), especially near and inside of neurovascular unit. The present study suggests that CCH activated both the coagulation and complement cascades in a novel AD model mice brain accompanied by the acceleration of AD pathology.",
keywords = "APP23 mice, Alzheimer's disease, blood–brain barrier, chronic cerebral hypoperfusion, coagulation, complement",
author = "Xiaowen Shi and Yasuyuki Ohta and Xia Liu and Jingwei Shang and R. Morihara and Yumiko Nakano and Tian Feng and Yong Huang and Kota Sato and Mami Takemoto and Nozomi Hishikawa and Toru Yamashita and Koji Abe",
note = "Funding Information: This work was partly supported by a Grant-in-Aid for Scientific Research (B) 17H0419619, (C) 15 K0931607, 17H0419619 and 17 K1082709, and by Grants-in-Aid from the Research Committees (Kaji R, Toba K, and Tsuji S) from Japan Agency for Medical Research and development (AMED) 7211700176, 7211700180 and 7211700095. X. S. would like to thank Otsuka Toshimi Scholarship Foundation for a scholarship support (18-235). Funding Information: This work was partly supported by a Grant-in-Aid for Scientific Research (B) 17H0419619, (C) 15?K0931607, 17H0419619 and 17?K1082709, and by Grants-in-Aid from the Research Committees (Kaji R, Toba K, and Tsuji S) from Japan Agency for Medical Research and development (AMED) 7211700176, 7211700180 and 7211700095. X. S. would like to thank Otsuka Toshimi Scholarship Foundation for a scholarship support (18-235). All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: K.A. Acquisition of data: X.S. X.L. J.S. Analysis and interpretation of data: X.S. X.L. J.S. Drafting of the manuscript: X.S. Y.O. Critical revision of the manuscript for important intellectual content: Y.O. K.A. Statistical analysis: X.S. Y.O. J.S. Obtained funding: K.A. Y.O. T.Y. Administrative, technical, and material support: X.S. Y.O. X.L. J.S. R.M. Y.N. T.F. Y.H. K.S. M.T. N.H. T.Y. Study supervision: K.A. The authors disclose no potential conflict of interests. Publisher Copyright: {\textcopyright} 2019 IBRO",
year = "2019",
month = sep,
day = "15",
doi = "10.1016/j.neuroscience.2019.07.050",
language = "English",
volume = "416",
pages = "126--136",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
}