Integrated late onset Alzheimer's disease (LOAD) susceptibility genes: Cholesterol metabolism and trafficking perspectives

Gene. 2017 Jan 15:597:10-16. doi: 10.1016/j.gene.2016.10.022. Epub 2016 Oct 20.

Abstract

Late onset Alzheimer's disease (LOAD) is the most common type of dementia and is characterized by decreased amyloid-β (Aβ) clearance from the brain. Cholesterol regulates the production and clearance of Aβ. Genome-wide association study (GWAS) suggests that at least 20 genes are associated with LOAD. The genes APOE, CLU, SORL1, PICALM, and BIN1 have a relatively high LOAD susceptibility. Additional experimental and bioinformatic approaches to integrate data from genetics, epigenetics, and molecular networks may further increase our understanding of LOAD in relation to cholesterol metabolism and trafficking.

Keywords: Alzheimer's disease; GWAS; LOAD; brain; cholesterol metabolism.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Biological Transport / genetics
  • Brain / metabolism*
  • Cholesterol / genetics*
  • Cholesterol / metabolism*
  • Clusterin / genetics
  • Clusterin / metabolism
  • Epistasis, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • LDL-Receptor Related Proteins / genetics
  • LDL-Receptor Related Proteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Monomeric Clathrin Assembly Proteins / genetics
  • Monomeric Clathrin Assembly Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Interaction Mapping
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Amyloid beta-Peptides
  • ApoE protein, human
  • Apolipoproteins E
  • BIN1 protein, human
  • CLU protein, human
  • Clusterin
  • LDL-Receptor Related Proteins
  • Membrane Transport Proteins
  • Monomeric Clathrin Assembly Proteins
  • Nuclear Proteins
  • PICALM protein, human
  • SORL1 protein, human
  • Tumor Suppressor Proteins
  • Cholesterol