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Studies on Alzheimer's Disease pp 119–135Cite as

Cholesterol Metabolism and Oxidative Stress in Alzheimer’s Disease

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Abstract

Cholesterol has a prominent role in cell structure and function, in the brain, including signal transduction, neurotransmitter release, synaptogenesis, and membrane trafficking. Perturbation of cholesterol trafficking in the brain is potentially linked to the pathogenesis of Alzheimer’s disease (AD). Cholesterol is unable to pass the blood–brain barrier, and its level in the brain depends exclusively on de novo synthesis and elimination, which rely on local transcription of ApoE and cassette transporters (ABCA1, ABCG1, and ABCG4) involved in the lipid transfer across membranes. These pathways are controlled by oxysterols. In order to maintain homeostasis, cholesterol is converted into 24-hydroxycholesterol by the neuronal specific cholesterol 24-hydroxylase, which is located in the endoplasmic reticulum. The putative role of upregulated oxidative stress in AD has raised interest in nonenzymatic oxysterols, which are generated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system and by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The analysis of oxysterols is a valuable tool to noninvasively investigating the role of cholesterol metabolism in the pathogenesis of neurodegeneration.

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Acknowledgments

The authors wish to gratefully acknowledge the collaboration along the years of Prof. I. Björkhem, Prof. U. Diczfalusy, Dr. A. Salomon, Prof. M. Kivipelto, Dr. M. Shafaati at Karolinska Insitutet, Stockholm, Sweden. The authors are grateful for discussion with all members of the European Network on Oxysterols Research (ENOR)(www.oxysterols.com). This work was supported by grants from Ministero dell’ Università, Ricerca Scientifica e Tecnologica (PRIN 2007L7BHK8) and Sapienza University of Rome (to L.I.); and Italian Ministry of Health (Fondi per giovani Ricercatori 2008) (to V.L.).

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  1. Laboratory of Vascular Medicine and Mass Spectrometry, Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, Corso della Republica 79, Rome, Italy

    Luigi Iuliano M.D.

  2. Laboratory of Clinical Pathology and Medical Genetics, Foundation IRCCS Institute of Neurology Carlo Besta, Milan, Italy

    Valerio Leoni M.D., Ph.D.

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  1. Luigi Iuliano M.D.
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  2. Valerio Leoni M.D., Ph.D.
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Correspondence to Luigi Iuliano M.D. .

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  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

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Iuliano, L., Leoni, V. (2013). Cholesterol Metabolism and Oxidative Stress in Alzheimer’s Disease. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_9

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