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Statins have therapeutic potential for the treatment of Alzheimer's disease, likely via protection of the neurovascular unit in the AD brain

  • Tomoko Kurata
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Hiromi Kawai
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Kazunori Miyazaki
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Miki Kozuki
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Nobutoshi Morimoto
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Yasuyuki Ohta
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Yoshio Ikeda
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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  • Koji Abe
    Correspondence
    Corresponding author at: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmacy, 2-5-1 Shikata-cho, Okayama 700‐8558, Japan. Tel.: +81 86 235 7365; fax: +81 86 235 7368.
    Affiliations
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700‐8558, Japan
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      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.

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