title: Isoform-specific effects of apoE on neurite outgrowth in olfactory epithelium culture.
abstract: BACKGROUND
  The apolipoprotein E4 (apoE4) genotype is a major risk factor for developing late-onset Alzheimer's disease (AD). Inheritance of apoE4 is also associated with impairments in olfactory function in early stages of AD. In this project we examined the effects of the three common isoforms of human apoE (apoE2, apoE3, and apoE4) on neuronal differentiation and neurite outgrowth in explant cultures of mouse olfactory epithelium (OE).
  
  
  RESULTS
  The OE cultures derived from apoE-deficient/knockout (KO) mice have significantly fewer neurons with shorter neurite outgrowth than cultures from wild-type (WT) mice. Treatment of the apoE KO culture with either purified human apoE2 or with human apoE3 significantly increased neurite outgrowth. In contrast, treatment with apoE4 did not have an effect on neurite outgrowth. The differential effects of human apoE isoforms on neurite outgrowth were abolished by blocking the low-density lipoprotein receptor-related protein (LRP) with lactoferrin and receptor-associated protein (RAP).
  
  
  CONCLUSIONS
  ApoE2 and apoE3 stimulate neurite outgrowth in OE cultures by interacting with the lipoprotein receptor, LRP. ApoE4, the isoform associated with AD, failed to promote neurite outgrowth, suggesting a potential mechanism whereby apoE4 may lead to olfactory dysfunction in AD patients.
authors.affiliation: Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA.
authors.forename: Aseem
authors.initials: A
authors.lastname: Hussain
authors.forename: Minh
authors.initials: M
authors.lastname: Luong
authors.forename: Apryl
authors.initials: A
authors.lastname: Pooley
authors.forename: Britto P
authors.initials: BP
authors.lastname: Nathan
mesh_terms: D000818:Animals; D053329:Apolipoprotein E2 / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020033:Protein Isoforms