Apolipoprotein E and apolipoprotein E receptors

normal biology and roles in Alzheimer disease.

David M. Holtzman, Joachim Herz, Guojun Bu

Research output: Contribution to journalArticle

Abstract

Apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer disease (AD); the ε4 allele increases risk and the ε2 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-β (Aβ) 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 Aβ 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 Aβ metabolism and toxicity. Therapeutic strategies based on apoE and apoE receptors may include influencing apoE/Aβ 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.

Original languageEnglish (US)
JournalCold Spring Harbor perspectives in medicine
Volume2
Issue number3
StatePublished - Mar 2012

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Low Density Lipoprotein Receptor-Related Protein-1
Apolipoproteins E
Alzheimer Disease
Neurology
Aptitude
LDL Receptors
Metabolism
Protein Isoforms
Central Nervous System
Alleles
Lipoprotein Receptors
Cell signaling
Neuronal Plasticity
Central Nervous System Diseases
HDL Lipoproteins
Lipid Metabolism
Amyloid
Neuroglia
Lipoproteins
Plasticity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Apolipoprotein E and apolipoprotein E receptors : normal biology and roles in Alzheimer disease. / Holtzman, David M.; Herz, Joachim; Bu, Guojun.

In: Cold Spring Harbor perspectives in medicine, Vol. 2, No. 3, 03.2012.

Research output: Contribution to journalArticle

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