Abstract
Structural and functional abnormalities in the neurovascular unit (NVU) have been
recently observed in Alzheimer's disease (AD). Statins, which are used clinically
for reducing cholesterol levels, can also exert beneficial vascular actions, improve
behavioral memory and reduce senile plaque (SP). Thus, we examined cognitive function,
the serum level of lipids, senile plaque (SP), and the protective effects of statins
on NVU disturbances in a mouse AD model. Amyloid precursor protein (APP) transgenic
(Tg) mice were used as a model of AD. Atorvastatin (30 mg/kg/day, p.o.) or pitavastatin (3 mg/kg/day, p.o.) were administered from 5 to 20 months of age. These 2 statins improved behavioral memory and reduced the numbers
of SP at 15 and 20 M without affecting serum lipid levels. There was a reduction in immunopositive staining
for N-acetyl glucosamine oligomer (NAGO) in the endothelium and in collagen IV in the APP
vehicle (APP/Ve) group, with collagen IV staining most weakest near SP. There was
also an increase in intensity and numbers of glial fibrillary acidic protein (GFAP)
positive astrocytes, particularly around the SP, where MMP-9 was more strongly labeled.
Double immunofluorescent analysis showed that astrocytic endfeet had detached from
the capillary endothelium in the APP/Ve group. Overall, these data suggest that statins
may have therapeutic potential for AD by protecting NVU.
Keywords
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Article info
Publication history
Published online: July 16, 2012
Accepted:
June 25,
2012
Received in revised form:
May 30,
2012
Received:
January 18,
2012
Identification
Copyright
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
