Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice.
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.
Park
In-Ho
IH
Brain Disease Research Center, Ajou University School of Medicine, Suwon, South Korea.
Hwang
Eun Mi
EM
Hong
Hyun Seok
HS
Boo
Jung Hyun
JH
Oh
Sang Soo
SS
Lee
Jeewoo
J
Jung
Min Whan
MW
Bang
Oh Young
OY
Kim
Seung U
SU
Mook-Jung
Inhee
I
D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000145:classification / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases; D015153:Blotting, Western; D001835:Body Weight; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism; D053764:Presenilin-1; D012737:Sex Factors; D013997:Time Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D002784:Cholesterol; D008148:Lovastatin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse