Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease

作者：Holtzman, David M.^*; Herz, Joachim; Bu, Guojun

来源：Cold Spring Harbor Perspectives in Medicine, 2012, 2(3): a006312.

DOI：10.1101/cshperspect.a006312

• DENSITY-LIPOPROTEIN RECEPTOR
• AMYLOID-BETA-PEPTIDE
• CENTRAL-NERVOUS-SYSTEM
• BLOOD-BRAIN-BARRIER
• HIPPOCAMPAL SYNAPTIC PLASTICITY
• GENOME-WIDE ASSOCIATION
• TRANSGENIC MOUSE MODEL
• PRECURSOR PROTEIN
• A-BETA
• PLAQUE-FORMATION

Apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer disease (AD); the epsilon 4 allele increases risk and the epsilon 2 allele is protective. In the central nervous system (CNS), apoE is produced by glial cells, is present in high-density-like lipoproteins, interacts with several receptors that are members of the low-density lipoprotein receptor (LDLR) family, and is a protein that binds to the amyloid-beta (A beta) peptide. There are a variety of mechanisms by which apoE isoform may influence risk for AD. There is substantial evidence that differential effects of apoE isoform on AD risk are influenced by the ability of apoE to affect A beta aggregation and clearance in the brain. Other mechanisms are also likely to play a role in the ability of apoE to influence CNS function as well as AD, including effects on synaptic plasticity, cell signaling, lipid transport and metabolism, and neuroinflammation. ApoE receptors, including LDLRs, Apoer2, very low-density lipoprotein receptors (VLDLRs), and lipoprotein receptor-related protein 1 (LRP1) appear to influence both the CNS effects of apoE as well as A beta metabolism and toxicity. Therapeutic strategies based on apoE and apoE receptors may include influencing apoE/A beta interactions, apoE structure, apoE lipidation, LDLR receptor family member function, and signaling. Understanding the normal and disease-related biology connecting apoE, apoE receptors, and AD is likely to provide novel insights into AD pathogenesis and treatment.

• 出版日期2012-3