- 作者: Aseem Hussain, Minh Luong, Apryl Pooley and Britto P Nathan
- 作者服務機構: Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, IL 61920, USA
- 中文摘要: --
- 英文摘要:
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).
Conclusion: 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. - 中文關鍵字: --
- 英文關鍵字: ApoE, Neurite outgrowth, Neuronal differentiation, Olfaction, Olfactory neurons, Lowdensity lipoprotein receptor-related protein, Receptor-associated protein, Alzheimer’s disease