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Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice.

Authors
Park, IH; Hwang, EM; Hong, HS; Boo, JH; Oh, SS; Lee, J; Jung, MW; Bang, OY; Kim, SU; Mook-Jung, I
Citation
Neurobiology of aging, 24(5):637-643, 2003
Journal Title
Neurobiology of aging
ISSN
0197-45801558-1497
Abstract
A recent clinical study showed that statins, which are inhibitors of cholesterol biosynthesis pathway, reduced the prevalence of Alzheimer's disease (AD). Animal studies that have employed high cholesterol diet indicate significant relationship between cholesterol level and senile plaque deposition. Here, we investigated the effects of lovastatin on beta-amyloid production and senile plaque deposition in an animal model of AD (Tg2576 mice). As expected, lovastatin treatment reduced plasma cholesterol level in both male and female mice. However, lovastatin enhanced the amounts of beta-amyloid and other beta-secretase derived peptides in females, but not in males. Likewise, lovastatin increased the number of plaques in the hippocampus and cortex of females, but not in males. Lovastatin did not change the amounts of full-length or alpha-secretase processed amyloid precursor protein (APP), or presenilin 1 (PS1) in either sex. Thus, lovastatin lowers cholesterol level in both genders, but enhances beta-amyloid production and senile plaque deposition only in brains of female Tg2576 mice. Our results suggest that low plasma cholesterol levels might be a risk factor for AD in females.
MeSH terms
Alzheimer Disease/metabolism*Amyloid Precursor Protein SecretasesAmyloid beta-Peptides/classificationAmyloid beta-Peptides/metabolism*Amyloid beta-Protein Precursor/metabolismAnimalsAnticholesteremic Agents/pharmacology*Aspartic Acid EndopeptidasesBlotting, WesternBody WeightCerebral Cortex/drug effectsCerebral Cortex/metabolismCholesterol/bloodDisease Models, AnimalEatingEndopeptidases/metabolismFemaleHippocampus/drug effectsHippocampus/metabolismHumansImmunohistochemistryLovastatin/pharmacology*MaleMembrane Proteins/metabolismMiceMice, TransgenicPlaque, Amyloid/drug effects*Plaque, Amyloid/metabolismPresenilin-1Sex FactorsTime Factors
PMID
12885571
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
박, 인호홍, 현석정, 민환방, 오영김, 승업묵, 인희
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