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Brain cholesterol, statins and Alzheimer's Disease.
Pharmacopsychiatry 2003; 36 Suppl 2:S113-9P

Abstract

Growing evidence suggests that cellular cholesterol homeostasis is causally involved in different steps leading to pathological events in the brain of Alzheimer's Disease (AD) patients. It was previously demonstrated that the processing of the amyloid beta-peptide precursor protein (APP) is modulated by pronounced alterations in cellular cholesterol levels using statins or cholesterol extracting agents. However, a cholesterol-rich diet was found to enhance amyloid beta-peptide (Abeta) burden in the brain of transgenic mice without clearly affecting total brain cholesterol levels. Recent retrospective epidemiological studies have reported that the use of statins potentially suppresses the development of AD. Although some HMG-CoA reductase inhibitors seem to influence the central cholesterol pool in vivo, the above epidemiological findings are probably not linked to statin-induced changes in brain membrane cholesterol levels per se since not all statins active in preventing AD enter the central nervous system (CNS). Recently, we reported that different statins, regardless of their brain availability, induce alterations in cellular cholesterol distribution in the brain. Such pleiotropic, cholesterol-synthesis independent statin effects might be indirect and are possibly mediated at the blood-brain barrier (BBB) via nitric oxide (NO) or apolipoprotein E (ApoE).

Authors+Show Affiliations

Department of Pharmacology, Biocenter Niederursel, University of Frankfurt, Frankfurt/M, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14574624

Citation

Kirsch, C, et al. "Brain Cholesterol, Statins and Alzheimer's Disease." Pharmacopsychiatry, vol. 36 Suppl 2, 2003, pp. S113-9.
Kirsch C, Eckert GP, Koudinov AR, et al. Brain cholesterol, statins and Alzheimer's Disease. Pharmacopsychiatry. 2003;36 Suppl 2:S113-9.
Kirsch, C., Eckert, G. P., Koudinov, A. R., & Müller, W. E. (2003). Brain cholesterol, statins and Alzheimer's Disease. Pharmacopsychiatry, 36 Suppl 2, pp. S113-9.
Kirsch C, et al. Brain Cholesterol, Statins and Alzheimer's Disease. Pharmacopsychiatry. 2003;36 Suppl 2:S113-9. PubMed PMID: 14574624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain cholesterol, statins and Alzheimer's Disease. AU - Kirsch,C, AU - Eckert,G P, AU - Koudinov,A R, AU - Müller,W E, PY - 2003/10/24/pubmed PY - 2003/12/12/medline PY - 2003/10/24/entrez SP - S113 EP - 9 JF - Pharmacopsychiatry JO - Pharmacopsychiatry VL - 36 Suppl 2 N2 - Growing evidence suggests that cellular cholesterol homeostasis is causally involved in different steps leading to pathological events in the brain of Alzheimer's Disease (AD) patients. It was previously demonstrated that the processing of the amyloid beta-peptide precursor protein (APP) is modulated by pronounced alterations in cellular cholesterol levels using statins or cholesterol extracting agents. However, a cholesterol-rich diet was found to enhance amyloid beta-peptide (Abeta) burden in the brain of transgenic mice without clearly affecting total brain cholesterol levels. Recent retrospective epidemiological studies have reported that the use of statins potentially suppresses the development of AD. Although some HMG-CoA reductase inhibitors seem to influence the central cholesterol pool in vivo, the above epidemiological findings are probably not linked to statin-induced changes in brain membrane cholesterol levels per se since not all statins active in preventing AD enter the central nervous system (CNS). Recently, we reported that different statins, regardless of their brain availability, induce alterations in cellular cholesterol distribution in the brain. Such pleiotropic, cholesterol-synthesis independent statin effects might be indirect and are possibly mediated at the blood-brain barrier (BBB) via nitric oxide (NO) or apolipoprotein E (ApoE). SN - 0176-3679 UR - https://www.unboundmedicine.com/medline/citation/14574624/Brain_cholesterol_statins_and_Alzheimer's_Disease_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2003-43058 DB - PRIME DP - Unbound Medicine ER -