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Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms.

Publication ,  Journal Article
Strittmatter, WJ
Published in: Biochem Soc Symp
2001

The three common apolipoprotein E (ApoE) alleles differentially contribute to the risk of Alzheimer's disease (AD). While the APOE genotype alters susceptibility to disease expression, individuals with APOE epsilon 4 alleles have the highest risk of developing AD; the APOE epsilon 4 allele is neither essential nor sufficient on its own to cause AD. Since the discovery, in 1992, of the involvement of APOE in AD, many scientists have explored the role of the ApoE isoforms in the central nervous system in an effort to elucidate their roles in the pathophysiological mechanism of this disease. While many hypotheses have been proposed, none has been proven. ApoE was discovered through investigations into cholesterol metabolism. In serum and in cerebrospinal fluid ApoE binds lipoprotein particles, which contain cholesterol esters, and is critical in the shuttling of cholesterol from cell to cell. Trafficking of ApoE is mediated by specific interactions with cell-surface receptors. As described later, several families of ApoE receptors with diverse functions have been discovered. The roles of these receptors are proving increasingly complex since additional interactions with other ligands and with other intracellular proteins are rapidly being identified. It was once thought that these receptors only shuttle ApoE-containing phospholipid particles from the extracellular environment into the cell, but they also transduce a number of additional intracellular signals and interactions. Molecular signalling cascades initiated by the various ApoE receptors modulate a number of critical cellular processes. To date, two functional classes of ApoE receptors have been identified. The first is the low-density lipoprotein receptor family and the second the scavenger receptor families.

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Published In

Biochem Soc Symp

DOI

ISSN

0067-8694

Publication Date

2001

Issue

67

Start / End Page

101 / 109

Location

England

Related Subject Headings

  • Signal Transduction
  • Scavenger Receptors, Class B
  • Receptors, Scavenger
  • Receptors, Lipoprotein
  • Receptors, LDL
  • Receptors, Immunologic
  • Nuclear Proteins
  • Nerve Tissue Proteins
  • Membrane Proteins
  • Low Density Lipoprotein Receptor-Related Protein-1
 

Citation

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Strittmatter, W. J. (2001). Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms. Biochem Soc Symp, (67), 101–109. https://doi.org/10.1042/bss0670101
Strittmatter, W. J. “Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms.Biochem Soc Symp, no. 67 (2001): 101–9. https://doi.org/10.1042/bss0670101.
Strittmatter WJ. Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms. Biochem Soc Symp. 2001;(67):101–9.
Strittmatter, W. J. “Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms.Biochem Soc Symp, no. 67, 2001, pp. 101–09. Pubmed, doi:10.1042/bss0670101.
Strittmatter WJ. Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms. Biochem Soc Symp. 2001;(67):101–109.

Published In

Biochem Soc Symp

DOI

ISSN

0067-8694

Publication Date

2001

Issue

67

Start / End Page

101 / 109

Location

England

Related Subject Headings

  • Signal Transduction
  • Scavenger Receptors, Class B
  • Receptors, Scavenger
  • Receptors, Lipoprotein
  • Receptors, LDL
  • Receptors, Immunologic
  • Nuclear Proteins
  • Nerve Tissue Proteins
  • Membrane Proteins
  • Low Density Lipoprotein Receptor-Related Protein-1