Characterization of Impaired Cerebrovascular Structure in APP/PS1 Mouse Brains

Kee Chan Ahn, Cameron R. Learman, Gary L. Dunbar, Panchanan Maiti, Won Cheoul Jang, Hyeon Cheol Cha, Mee Sook Song

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood–brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD. We previously reported that astrocytes, essential components of BBB, were chronically activated and some deteriorated in the brain of 5xFAD, an amyloid precursor protein/presenilin1 (APP/PS1) transgenic mouse model. Thus, it is rational to investigate if any vascular dysfunction is associated with considerable activation of astrocytes in APP/PS1 mouse model. In this study, we observed that cerebrovascular pathology was associated with large scale of reactive astrocytes and neurodegeneration in an Aβ plague-generating mouse model. Using 5xFAD mouse brains, we demonstrate damaged brain vessels and reduced expression of glucose transporter 1 (GLUT1), the main glucose transporter, and a tight junction protein zonula occludens-1 (ZO-1) of cerebrovascular endothelial cells. This vascular pathology was closely associated with astrocytic deterioration and neuronal loss due to buildup of Aβ plaques in 5xFAD mouse brains.

Original languageEnglish
Pages (from-to)246-254
Number of pages9
JournalNeuroscience
Volume385
DOIs
StatePublished - Aug 10 2018

Keywords

  • Alzheimer's disease
  • blood brain barrier
  • cerebrovascular impairment
  • neurodegeneration
  • reactive astrocyte

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