The cholesterol-fed rabbit as a model system for cholesterol-Alzheimer's disease studies

R. P.Jaya Prasanthi, Gurdeep Marwarha, Othman Ghribi

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Epidemiological, animal, and cellular studies suggest that abnormalities in cholesterol metabolism are a risk factor for Alzheimer's disease (AD), potentially by increasing amyloid-β (Aβ) peptide levels. Accumulation of Aβ in the brain is suggested to play a key role in the neurodegenerative processes by triggering the hyperphosphorylation of tau and the neuronal death that develop in the course of AD. However, the mechanisms by which cholesterol increases Aβ levels are still ill-defined. Work from our laboratory using the cholesterol-fed rabbit model system indicates that hypercholesterolemia increases Aβ through multiple mechanisms that affect production, degradation and clearance of this peptide. We also have found that the oxidized cholesterol metabolite, 27-hydroxycholesterol, also increases Aβ levels in organotypic slices from rabbit hippocampus. Our results suggest that multiple signaling pathways are involved in hypercholesterolemia-induced AD pathology and suggest 27-hydroxycholesterol as the link between circulating cholesterol and AD-like pathology in the brain.

Original languageEnglish (US)
Title of host publicationHandbook of Animal Models in Alzheimer's Disease
EditorsGemma Casadesus
Pages163-178
Number of pages16
DOIs
StatePublished - Dec 1 2011

Publication series

NameAdvances in Alzheimer's Disease
Volume1
ISSN (Print)2210-5727
ISSN (Electronic)2210-5735

Keywords

  • 27-hydroxycholesterol
  • Alzheimer's disease
  • amyloid-β
  • cholesterol
  • rabbit

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Prasanthi, R. P. J., Marwarha, G., & Ghribi, O. (2011). The cholesterol-fed rabbit as a model system for cholesterol-Alzheimer's disease studies. In G. Casadesus (Ed.), Handbook of Animal Models in Alzheimer's Disease (pp. 163-178). (Advances in Alzheimer's Disease; Vol. 1). https://doi.org/10.3233/978-1-60750-733-8-163