Klaus Faßbender1, Mikael Simons1, Christine Bergmann1, Mark Stroick1, Dieter Lütjohann1,2, Patrick Keller3,1, Heiko Runz1, Sandra Kühl1,2, Thomas Bertsch1, Klaus von Bergmann1, M.G. Hennerici1, Konrad Beyreuther1, Tobias Hartmann1
1Departments of Neurology and Clinical Chemistry, Clinic
Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167
Mannheim, Germany; Department of Neurology, University
of Tübingen, Hoppe-Seyler Strasse 3, D-72076 Tübingen,
Germany; Center for Molecular Biology Heidelberg
(ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, D-69120
Heidelberg, Germany; Department of Clinical
Pharmacology, University of Bonn, Sigmund-Freud-Strasse 25, 53105
Bonn, Germany; and Cell Biology...
2Max Planck Institute for Medical Research, Heidelberg, Germany
3Cell Biology Program, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69012 Heidelberg, Germany
Tóm tắt
Recent epidemiological studies show a strong reduction in the
incidence of Alzheimer's disease in patients treated with
cholesterol-lowering statins. Moreover, elevated Aβ42 levels and the
ɛ4 allele of the lipid-carrier apolipoprotein E are regarded as risk
factors for sporadic and familial Alzheimer's disease. Here we
demonstrate that the widely used cholesterol-lowering drugs simvastatin
and lovastatin reduce intracellular and extracellular levels of Aβ42
and Aβ40 peptides in primary cultures of hippocampal neurons and
mixed cortical neurons. Likewise, guinea pigs treated with high doses
of simvastatin showed a strong and reversible reduction of cerebral
Aβ42 and Aβ40 levels in the cerebrospinal fluid and brain
homogenate. These results suggest that lipids are playing an important
role in the development of Alzheimer's disease. Lowered levels of
Aβ42 may provide the mechanism for the observed reduced incidence of
dementia in statin-treated patients and may open up avenues for
therapeutic interventions.
