Differential effects of lovastatin treatment on brain cholesterol levels in normal and ApoE-deficient mice
- 1 April 2001
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in NeuroReport
- Vol. 12 (5), 883-887
- https://doi.org/10.1097/00001756-200104170-00003
Abstract
Growing evidence indicates that membrane cholesterol is involved in the development of Alzheimer's disease. Therefore, the availability of pharmacological strategies to modify brain cholesterol is of increasing importance. Accordingly, we investigated the effects of the HMG-CoA reductase inhibitor lovastatin on brain cholesterol levels in vivo. Brain cholesterol was significantly decreased by lovastatin treatment (100 mg/kg/day) in 1- and 12-month-old C57BL/6J mice. Reduced brain cholesterol was associated with decreased pyrene-excimer fluorescence, indicating altered membrane function. Lovastatin had no effect on brain cholesterol in ApoE−/− mice. Peripheral cholesterol levels were not affected by lovastatin in all three groups of mice. We demonstrate for the first time that lovastatin represents a valid pharmacological tool to significantly modulate brain cholesterol levels.Keywords
This publication has 23 references indexed in Scilit:
- Cholesterol Modulates the Membrane- Disordering Effects of Beta-Amyloid Peptides in the Hippocampus: Specific Changes in Alzheimer’s DiseaseDementia and Geriatric Cognitive Disorders, 2000
- Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathwayBiochemical Journal, 2000
- The role of cholesterol in the biosynthesis of β-amyloid.NeuroReport, 1999
- Recent advances in brain cholesterol dynamics: Transport, domains, and Alzheimer's diseaseLipids, 1999
- Amyloid and lipids in the pathology of Alzheimer diseaseAmyloid, 1999
- Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neuronsProceedings of the National Academy of Sciences, 1998
- Cholesterol Modulates α-Secretase Cleavage of Amyloid Precursor ProteinJournal of Biological Chemistry, 1996
- Apolipoprotein E and Cholesterol Affect Neuronal Calcium Signaling: The Possible Relationship to β-Amyloid NeurotoxicityBiochemical and Biophysical Research Communications, 1994
- Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's diseaseNeurology, 1993
- Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell BiologyScience, 1988