Journal of Molecular Neuroscience

, Volume 20, Issue 3, pp 395–406 | Cite as

Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol

  • Suzana S. Petanceska
  • Steven DeRosa
  • Ali Sharma
  • Nichole Diaz
  • Karen Duff
  • Steven G. Tint
  • Lorenzo M. Refolo
  • Miguel Pappolla
Alzheimer’s Therapeutics: Lipid Lowering


Apolipoprotein E (ApoE) influences the risk of late onset Alzheimer’s disease (AD) in an isoform-dependent manner, such that the presence of the apoE ε4 allele increases the risk of AD while the presence of the apoE ε2 allele appears to be protective. Although a number of ApoE functions are isoform dependent and may underlie the “risk factor” activity of AD, its ability to bind amyloid β peptides and influence their clearance and/or deposition has gained strong experimental support. Evidence suggests that in addition to genotype, increased ApoE transcription can contribute to AD risk. There is growing evidence in support of the hypothesis that disrupted cholesterol metabolism is an early risk factor for AD. Studies in animal models have shown that chronic changes in cholesterol metabolism associate with changes in brain Aβ accumulation, a process instrumental for establishing AD pathology. ApoE mediates cholesterol homeostasis in the body and is a major lipid carrier in brain. As such, its expression in the periphery and in brain changes in response to changes in cholesterol metabolism. Here, we used a transgenic mouse model of Alzheimer’s amyloidosis to examine whether the diet-induced or pharmacologically induced changes in plasma cholesterol that result in altered brain amyloidosis also affect ApoE content in liver and in brain. We found that chronic changes in total cholesterol in plasma lead to changes in ApoE mRNA levels in brain. We also found that cholesterol loading of primary glial cells increases cellular and secreted ApoE levels and that long-term treatment of astrocytes and microglia with statins leads to a decrease in the cellular and/or secreted ApoE. These observations suggest that disrupted cholesterol metabolism may increase the risk of developing AD in part due to the effect of cholesterol on brain ApoE expression.

Index Entries

Alzheimer’s disease ApoE cholesterol statin transgenic mice 


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Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Suzana S. Petanceska
    • 1
    • 2
  • Steven DeRosa
    • 1
  • Ali Sharma
    • 1
  • Nichole Diaz
    • 1
  • Karen Duff
    • 1
    • 2
  • Steven G. Tint
    • 3
  • Lorenzo M. Refolo
    • 4
  • Miguel Pappolla
    • 5
  1. 1.Center for Dementia ResearchNathan Kline InstituteOrangeburg
  2. 2.Department of PsychiatryNYU Medical CenterNew York
  3. 3.University of Medicine and Dentistry of New Jersey
  4. 4.Institute for the Study of AgingNew York
  5. 5.University of South AlabamaMobile

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