Bilateral implantation of shear stress modifier in ApoE knockout mouse induces cognitive impairment and tau abnormalities

Shuke Nie, Yang Tan, Zhentao Zhang, Guiqin Chen, Jing Xiong, Dan Hu, Keqiang Ye, Yunjian Zhang, Xuebing Cao, Liam Chen, Zhaohui Zhang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Vascular cognitive impairment (VCI) encompasses all causes of cerebrovascular disease that lead to cognitive decline, or overt dementia, atherosclerotic disease being the most common contributor. However, few rodent models that mimic the pathology of VCI replicated the clinical cerebrovascular atherosclerosis. Here we aimed to investigate the mechanism underlying VCI in an Apolipoprotein E knockout (ApoE-KO) mouse model fed with western style food with implantation of bilateral shear stress modifiers. We established a cognitive decline in spatial learning and memory developed in the bilateral modifier treated mice. Brain imaging and pathological examinations demonstrated reduced glucose intake and neuronal loss in hippocampus. Although no amyloid plaques or neurofibrillary tangles (NFTs) were observed, tau pathology including hyperphosphorylation, paired helical filament formation and pathologic truncation were found at considerable higher extent in the bilateral modifier group 8 weeks post the procedure. In addition, gliosis and microglia activation were confirmed in corpus callosum (CC) and ventral striatum. Thus, this ApoE-KO mouse model faithfully replicates the stenosis of common carotid artery (CCA) and cognitive impairment following atherosclerotic deposition and global cerebral hypoperfusion. The close correlation of cognitive decline and tau pathology indicates the toxic tau species could be at least partially responsible for the neurodegenerative changes induced by the chronic hypoxia/ischemia.

Original languageEnglish (US)
Article number303
JournalFrontiers in Aging Neuroscience
Issue numberOCT
StatePublished - Oct 4 2018
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Johns Hopkins School of Medicine startup fund to LC; National Natural Science Foundation of China (NSFC Project No. 81701257 and No. 81671051) and the Foundation of Independent Research Projects of Wuhan University (2042017kf0050) to SN and Z-HZ.

Publisher Copyright:
© 2018 Nie, Tan, Zhang, Chen, Xiong, Hu, Ye, Zhang, Cao, Chen and Zhang.


  • Asparagine endopeptidase
  • Atherosclerosis
  • Shear stress modifier
  • Tau
  • Vascular cognitive impairment


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