Function of β‐amyloid in cholesterol transport: a lead to neurotoxicity

  title={Function of $\beta$‐amyloid in cholesterol transport: a lead to neurotoxicity},
  author={Z X Yao and Vassilios Papadopoulos},
  journal={The FASEB Journal},
Amyloid β‐peptide (Aβ), Aβ precursor protein (APP), apolipoprotein E (apoE), and elevated cholesterol levels have been linked to Alzheimer's disease (AD) pathology. High cholesterol levels increase APP and apoE expression in human NT2 neuron progenitor cells. A cholesterol‐ rich environment also induces processing of APP, leading to the formation of Aβ and Aβ peptide fragments. Using a novel method, we determined that 1) cholesterol binds to Aβ at a‐secretase cleavage site; 2) Aβ17–40 rather… 
Regulation of cholesterol efflux by amyloid β secretion
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Oxidation of Cholesterol by Amyloid Precursor Protein and β-Amyloid Peptide*
It is shown that both β-amyloid and APP can oxidize cholesterol to form 7β-Hydroxycholesterol, a proapoptotic oxysterol that was neurotoxic at nanomolar concentrations and suggest that a function of APP may be to produce low levels of 7-hydroxych cholesterol.
Lipids in Amyloid-β Processing, Aggregation, and Toxicity.
The roles of specific lipids, lipid assemblies and apolipoprotein E in Aβ processing, clearance and aggregation are overviewed and the contribution of these factors to the neurotoxicity in AD is discussed.
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Genetic, neuropathological and biochemical studies suggest strong links between cholesterol, the apolipoprotein E (APOE) and Alzheimer’s disease (AD), both in humans and in animal models of the
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The complex association of cholesterol metabolism and Alzheimer's disease is presented in depth, including the possible benefits to be gained from cholesterol-lowering statin therapy. Then follows a
Role of Cholesterol in APP Metabolism and Its Significance in Alzheimer’s Disease Pathogenesis
Current understanding on the role of cholesterol in regulating the production/function of Aβ-related peptides is summarized and the therapeutic potential of regulating cholesterol homeostasis in the treatment of AD pathology is examined.
Platelet-activating factor antagonists enhance intracellular degradation of amyloid-β42 in neurons via regulation of cholesterol ester hydrolases
Results are consistent with the hypothesis that the Aβ-induced production of PAF controls a cholesterol-sensitive pathway that affects the cellular localization and hence the fate of Aβ42 in neurons and conclude that the targeting of A β42 to rafts in normal cells is a factor that affects its degradation.
Why is the amyloid beta peptide of Alzheimer's disease neurotoxic?
  • A. Rauk
  • Biology
    Dalton transactions
  • 2008
In this article, we support the case that the neurotoxic agent in Alzheimer's disease is a soluble aggregated form of the amyloid beta peptide (Abeta), probably complexed with divalent copper. The


Modulation of Secreted β-Amyloid Precursor Protein and Amyloid β-Peptide in Brain by Cholesterol*
It is demonstrated that secreted APP processing derivatives and Aβ can be modulated in the brain of an animal by diet and evidence that cholesterol plays a role in the modulation of APP processing in vivo is provided.
Amyloid beta peptide alters intracellular vesicle trafficking and cholesterol homeostasis.
It is shown that both Abeta and submicromolar concentrations of free cholesterol alter the trafficking of a population of intracellular vesicles that are involved in the transport of the reduced form of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetazolium bromide (MTT formazan), the formation of which is a widely used cell viability assay.
Cholesterol Modulates -Secretase Cleavage of Amyloid Precursor Protein (*)
The current conclusion suggests that changes in cellular cholesterol levels in Alzheimer's disease could contribute to neuronal degeneration by decreasing the production of APP.
Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons.
It is shown that cholesterol is required for Abeta formation to occur and imply a link between cholesterol, Abeta, and Alzheimer's disease.
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Differences in the two isoforms in complexing with the beta/A4 peptide may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease.
Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway.
The results indicate that cholesterol decreases the secretion of APPs by interfering with APP maturation and inhibiting glycosylation of the protein; although APP is inserted in the membrane it is not cleaved by alpha-secretase.
Association of human, rat, and rabbit apolipoprotein E with β‐amyloid
Aβ binding to lipoprotein‐associated and purified apoE2 provides one possible explanation for protective effects of both apo E2 and E3 against the development of Alzheimer's disease.
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The results suggest a possible involvement of apoE3 in the clearance or routing out of Abeta from the central nervous system as one of the mechanisms underlying the pathology of the disease.
Hypercholesterolemia Accelerates the Alzheimer's Amyloid Pathology in a Transgenic Mouse Model
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