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P3‐391: Statins for the treatment of dementia
Author(s) -
McGuinness Bernadette,
O'Hare John,
Bullock Roger,
Malouf Reem,
Craig David,
Passmore Peter
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1933
Subject(s) - medicine , dementia , placebo , statin , cochrane library , vascular dementia , meta analysis , randomized controlled trial , physical therapy , disease , pathology , alternative medicine
analysis), and lactate dehydrogenase (LDH) for cell death. Labelling the cells with anti-CD-11b (OX-42) enabled microglia morphology to be visualised under microscopy for qualitative assessment of activation. Results: Findings from these experiments showed that AHPN (5-100 mM) decreased LPSmediated production of NO2 but not cytokines. Western immunoblotting demonstrated a significant attenuation of phosphorylated nuclear factor kappa B (NF-kB) and iNOS by 5 mM AHPN. Microscopy analysis of CD-11b-positive cells indicated that 5 mM AHPN reverted LPS-induced activated morphologies whilst reducing cell number through Cyclin D1 inhibition. However, higher concentrations of AHPN (50-100 mM) induced cell death through increased LDH accumulation and condensation of nuclei (through Hoechst dye staining). Preliminary results also indicated that production of NO2 by Ab1-42 (+ IFN-g) was reduced by AHPN. Conclusions: Taken together, the results show that microglial activation can be attenuated by AHPN, as evidenced by the inhibition of both proliferation and NO2 production through reduced NF-kB activation and iNOS production. In conclusion, these new findings provide a possible antiinflammatory role for synthetic retinoids, which could be a useful therapeutic strategy for neurodegenerative diseases that involve an inflammatory component, such as AD.