Apolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities

A Cedazo‐Mínguez - Journal of cellular and molecular …, 2007 - Wiley Online Library
Journal of cellular and molecular medicine, 2007Wiley Online Library
• Introduction• ApoE function• ApoE role in AD pathology–ApoE and Aβ–ApoE and
neurofibrillary tangles–ApoE, cholesterol and synaptic repair–ApoE and cholinergic
dysfunction–ApoE and signalling–ApoE and neurotoxicity• ApoE as a therapeutic target for
AD• Conclusions Abstract Multiple genetic and environmental factors are likely to contribute
to the development of Alzheimer's disease (AD). The most important known risk factor for AD
is presence of the E4 isoform of apolipoprotein E (apoE). Epidemiological studies …
  • • 
    Introduction
  • • 
    ApoE function
  • • 
    ApoE role in AD pathology
    • – 
      ApoE and Aβ
    • – 
      ApoE and neurofibrillary tangles
    • – 
      ApoE, cholesterol and synaptic repair
    • – 
      ApoE and cholinergic dysfunction
    • – 
      ApoE and signalling
    • – 
      ApoE and neurotoxicity
  • • 
    ApoE as a therapeutic target for AD
  • • 
    Conclusions
Abstract
Multiple genetic and environmental factors are likely to contribute to the development of Alzheimer's disease (AD). The most important known risk factor for AD is presence of the E4 isoform of apolipoprotein E (apoE). Epidemiological studies demonstrated that apoE4 carriers have a higher risk and develop the disease and an early onset. Moreover, apoE4 is the only molecule that has been associated with all the biochemical disturbances characteristic of the disease: amyloid‐beta (Aβ) deposition, tangle formation, oxidative stress, lipid homeostasis deregulation, synaptic plasticity loss and cholinergic dysfunction. This large body of evidence suggest that apoE is a key player in the pathogenesis of AD. This short review examines the current facts and hypotheses of the association between apoE4 and AD, as well as the therapeutic possibilities that apoE might offer for the treatment of this disease.
Wiley Online Library