Zusammenfassung
In zwei rezenten Beobachtungsstudien wurde eine um 60-73% erniedrigte Prävalenz der Alzheimer-Krankheit bei Patienten unter Statintherapie beobachtet. In zwei weiteren Studien wurde gezeigt, daß ein bestimmter Polymorphismus im Cyp46-Gen, welches die Cholesterin-24-Hydroxylase kodiert, das Risiko für eine Alzheimerkrankheit mit Spätbeginn signifikant erhöht. Daraus ergibt sich die Frage, ob Statine als Prophylaktikum gegen Alzheimer eingesetzt werden können. Statine passieren die Blut-Hirn-Schranke in unterschiedlicher Quantität und bewirken eine Reduktion des zerebralen Cholesterin-Umsatzes. Sie können auch die Liquor-Konzentration von Tau und, wenn auch nur in geringem Maß, jene von Aß beeinflussen. Es muß in weiteren Studien festgestellt werden, welche Statine sich am besten für die Beeinflussung des zerebralen Amyloid-metabolismus eignen und eventuell auch das Risiko bzw. den Schweregrad der Alzheimer-Krankheit beeinflussen können.
Summary
Two recent observational studies have demonstrated a 60–73% reduction in the prevalence of Alzheimer’s disease in patients treated with statins. In two further studies a polymorphism in the CYP46 gene encoding the cholesterol-24 hydroxylase was found to be associated with a significant increase in the risk of late-onset Alzheimer’s disease. The question arises whether or not statins may exert a prophylactic effect on the incidence of Alzheimer’s disease. Statins pass the blood-brain-barrier to a different degree and may reduce the cerebral cholesterol turnover. Statins may also influence the CSF concentration of tau protein, and, to a minor extent, that of Aß. Further studies are warranted to find out which statins are most suitable for reducing cerebral amyloid metabolism and whether statins may also lower the severity of Alzheimer’s disease.
This is a preview of subscription content, log in via an institution to check access.
Literatur
Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A: Non lipid-related-effects of statins Ann Med 2000;32:164–176.
Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J: Cholesterol homeostasis in human brain: turnover of 24S-hydroxy-cholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 1998;39:1594–1600.
Bogdanovic N, Bretillon L, Lund EG, Diczfacusy U. Lannfelt L, Winblad B, Russell DW, Bjorkhem I: On the turnover of brain cholesterol in patients with Alzheimer’s disease: abnormal induction of the cholesterolcatabolic enzyme CYP46 in glial cells. Neurosci Lett 2001;314:45–48.
Fassbender K, Simons M, Bermann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther Km, Hartmann T: Simvaslatin strongly reduces Alzheimer’s diseases Aß 42 and Aß 40 levels in vitro and in vivo. Proc Natl Acad Sci U.S.A. 2001;98:5856–5861.
Haley RW: Is the a Connection between the Concentration of Cholesterol Circulatiing in Plasma and the Rate of Neuritic Plaque Formation in Alzheimer Disease? Arch Neurol 2000;57:1410–1412.
Hartmann T: Cholesterol, Aß und Alzheimer’s disease. TINS 2001: 24(Suppl):45–48.
Jick H, Zornberg GL, Jick SS, Seshadri D, Drachman DA: Statins and the risk of dementia. Lancet 2000;356:1627–1631.
Kölsch H, Luthohann D, Ludwig M, Schulte A, Ptok U, Jessen F, von Bergmann K, Raom L, Maier W, Heun R: Polymorphism in the cholesterol 24S-hydroxylase gene in associated with Alzheimer’s disease. Mol Psychiatry 2002;7:899–902.
Papassotiropoulos A, Streffer JR, Tsolaki M, Schmid S, Thal D, Nicosia F, Lakovidou V, Maddalena A, Lutjohann D, Ghebremidhin E, Hgei T, Pasch T, Träxler M, Brühl A, Benussi L, Binetti G, Braak H, Nitsch RM, Hock C: Increased Brain ß — Amyloid Load, Phosphorylated Tau, and Risk of Alzheimer Disease Associated with an Intronic CYP46 Polymorphism, Arch Neurol 2003;60:29–35.
Petanceska SS, DeRosa S, Olm V, et al: Statin therapy for Alzheimer’s disease: will it work? J Mol Neurosci 2002;19:155–161.
Refolo LM, Pappolla MA, Malester B, et al: Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000;7:321–331.
Simons M, Keller P, De Stropper B, et al: Cholesterol depletion inhibits the generation of ß-amyloid in hippocampal neurons. Proc Natl Acad Sci U.S.A 1998;(95):6460–6464.
Simons M, Keller P, Dichtgans J, Schulz JB: Cholesterol and Alzheimer’s disease: is there a link? Neurology 2001;57:1089–1093.
Simons M, Schwarzler F. Lutjohann D, et al: Treatment with simvastatin in normochlesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 2002;52:346–350.
Sparks DL, Kuo YM, Roher A, Martin T, Lukas RJ: Alterations of Alzheimer’s disease in the cholesterol-fed rabbit, including vascular inflammation: preliminary observations. Ann NY Acad Sci 2000;903:335–344.
Strittmatter WJ, Saunders AM, Schmechel D, et al: Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 1993;90:1977–1981.
Van Haelst PL, Van Doormaal JJ, May JF, Gans ROB, Crijns HJGM, Cohen Tervaert JW: Secondary prevention with fluvastatin decreases levels of adhesion molecules, neopterin and C-reactive protein. Europ. Journ.of Int. Med 2001;12:503–509.
Wolozin B, Kjellman W, Ruosseau P, Celesia GG, Siegel G: Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439–1443.
Wolozin B: Cyp46 (24S-Cholesterol Hydoxlase). A Genetic Risk Factor for Alzheimer Disease, Arch Neurol 2003;60:16–18.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ransmayr, G. Cholesterin und Statine beim Morbus Alzheimer. WMW 153, 258–259 (2003). https://doi.org/10.1046/j.1563-258X.2003.03031.x
Issue Date:
DOI: https://doi.org/10.1046/j.1563-258X.2003.03031.x