Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice

Xiaowen Shi, Yasuyuki Ohta, Xia Liu, Jingwei Shang, R. Morihara, Yumiko Nakano, Tian Feng, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Koji Abe

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)126-136
Number of pages11
JournalNeuroscience
Volume416
DOIs
Publication statusPublished - Sep 15 2019

Fingerprint

Factor XIII
Alzheimer Disease
Pathology
Complement C1 Inhibitor Protein
Complement C3
Neocortex
Brain
Thalamus
Amyloid
Fibrinogen
Hippocampus

Keywords

  • Alzheimer's disease
  • APP23 mice
  • blood–brain barrier
  • chronic cerebral hypoperfusion
  • coagulation
  • complement

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice. / Shi, Xiaowen; Ohta, Yasuyuki; Liu, Xia; Shang, Jingwei; Morihara, R.; Nakano, Yumiko; Feng, Tian; Huang, Yong; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi; Yamashita, Toru; Abe, Koji.

In: Neuroscience, Vol. 416, 15.09.2019, p. 126-136.

Research output: Contribution to journalArticle

Shi, Xiaowen ; Ohta, Yasuyuki ; Liu, Xia ; Shang, Jingwei ; Morihara, R. ; Nakano, Yumiko ; Feng, Tian ; Huang, Yong ; Sato, Kota ; Takemoto, Mami ; Hishikawa, Nozomi ; Yamashita, Toru ; Abe, Koji. / Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice. In: Neuroscience. 2019 ; Vol. 416. pp. 126-136.
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