Investigating the effects of APOE-£4 on angiogenesis and blood brain barrier integrity in early stages of cerebrovascular development

Larisa Kavetsky

Document Type

Article

Publication Date

Summer 2018

JAX Location

In: Student Reports, Summer 2018, The Jackson Laboratory

Abstract

Although there are many forms of dementia, vascular dementia is gaining attention because of the contributions that vascular health can have on the development of dementia. In this study, analysis of transverse and coronal images of the developing mouse brain has confirmed the best method for visualizing embryonic brain vasculature. Throughout this study, we use immunohistochemistry to understand the physiological phenomena occurring as early as the embryonic stages and how tl1e Apoe gene may be affecting development. The goals of this study are to understand the mechanism of angiogenesis and look for the presence of astrocytes and microglia~ two types of cells suspected of expressing Apoe. These findings will allow us to speculate how eacl1 may play a role in the development of the embryonic brain vasculature. This study further opens tlp potential for investigating how, if present, human Apoe genotype (hApoe) expression from microglia and astrocytes at emb:ryonic day 15 (El5) could lead to early signs of development of Alzheimer's Disease or dementia. In the future, we will compare the amount of microglia and astrocytes present across three genotypes (hApoee3h 3, hApoee3te4, and hApoee4te4) to detect noticeable differences in development of vasculature in the brain of embryonic mice to possibly support the hypothesis that Apoem, the greatest genetic rislc factor for late onset Alzheimer's Disease1, affects vascular development long before typical phenotypes of AD and dementia are detected.

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