Degree Name

Master of Science (MS)

Semester of Degree Completion

2000

Thesis Director

Britto P. Nathan

Abstract

Apolipoprotein (apo) E4, one of the three common isoforms of apoE, has been implicated in Alzheimer's disease (AD). The mechanism whereby apoE4 leads to the pathogenesis of AD is unknown. In the present study, I examined the effects of apoE on neurite outgrowth from adult mice cortical neurons (AMC) in culture. I found that neurite outgrowth from AMC neurons derived from apoE deficient/apoE gene knockout (apoE KO) mice is significantly shorter than that from age-, sex-, and strain-matched wild-type control mice. Furthermore, I present evidence for the differential effects of two isoforms of human apoE, apoE3 and apoE4, on neurite outgrowth from apoE KO neurons. Human apoE3 enhances neurite outgrowth whereas human apoE4 inhibits outgrowth. The differential effects of apoE3 and apoE4 on neurite outgrowth appear to be mediated by the low-density lipoprotein receptor related protein (LRP). Blocking of the LRP pathway of lipoprotein uptake with lactoferrin and receptor associated protein (RAP) abolished the differential effects of apoE isoforms on neurite outgrowth. Further understanding of the isoform specific cell biological processes mediated by apoE-LRP interactions in AMC culture may provide insight into AD pathogenesis.

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