title: Apolipoprotein E Isoforms and AMD.
abstract: The cholesterol transporting protein apolipoprotein E (ApoE) occurs in three allelic variants in humans unlike in other species. The resulting protein isoforms E2, E3 and E4 exhibit differences in lipid binding, integrating into lipoprotein particles and affinity for lipoprotein receptors. ApoE isoforms confer genetic risk for several diseases of aging including atherosclerosis, Alzheimer's disease, and age-related macular degeneration (AMD). A single E4 allele increases the risk of developing Alzheimer's disease, whereas the E2 allele is protective. Intriguingly, the E4 allele is protective in AMD. Current thinking about different functions of ApoE isoforms comes largely from studies on Alzheimer's disease. These data cannot be directly extrapolated to AMD since the primary cells affected in these diseases (neurons vs. retinal pigment epithelium) are so different. Here, we propose that ApoE serves a fundamentally different purpose in regulating cholesterol homeostasis in the retinal pigment epithelium and this could explain why allelic risk factors are flipped for AMD compared to Alzheimer's disease.
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 1300 University Ave, SMI 677, 53706, Madison, WI, USA. toops@wisc.edu.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Toops
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 1300 University Ave, SMI 677, 53706, Madison, WI, USA. ltan8@wisc.edu.
authors.forename: Li Xuan
authors.initials: LX
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 1300 University Ave, SMI 677, 53706, Madison, WI, USA. lakkaraju@wisc.edu.|McPherson Eye Research Institute, University of Wisconsin-Madison, 53706, Madison, WI, USA. lakkaraju@wisc.edu.|Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 53706, Madison, WI, USA. lakkaraju@wisc.edu.
authors.forename: Aparna
authors.initials: A
authors.lastname: Lakkaraju
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D053329:Apolipoprotein E2 / Q000235:genetics / Q000378:metabolism*; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D012307:Risk Factors
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D008074:Lipoproteins; D011973:Receptors, LDL; D002784:Cholesterol
keywords: Age-related macular degeneration; ApoE isoforms; Apolipoprotein E; Cholesterol; Retinal pigment epithelium