A novel Aβ-fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice.
Bottom Line: To determine if the Aβ-fibrinogen interaction could be targeted as a potential new treatment for AD, we designed a high-throughput screen and identified RU-505 as an effective inhibitor of the Aβ-fibrinogen interaction.Furthermore, long-term treatment of RU-505 significantly reduced vascular amyloid deposition and microgliosis in the cortex and improved cognitive impairment in mouse models of AD.Our studies suggest that inhibitors targeting the Aβ-fibrinogen interaction show promise as therapy for treating AD.
Affiliation: Laboratory of Neurobiology and Genetics and High Throughput Screening Resource Center, The Rockefeller University, New York, NY 10065.Show MeSH
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Mentions: Therefore, we measured the level of infiltrated fibrinogen and microgliosis in the cortex of Tg6799 or WT littermate mice after RU-505 treatment. We quantified fibrinogen deposition (green; Fig. 7 A) outside the endothelial cells of blood vessels that were labeled using CD31 (red; Fig. 7 A), and the area of activated microglia that were labeled using CD11b (red; Fig. 7 B). The levels of infiltrated fibrinogen and microgliosis were highly increased in the cortex of Tg6799 compared with WT mice (Fig. 7, C and D), and these increases were significantly decreased by RU-505 (Fig. 7, C and D).
Affiliation: Laboratory of Neurobiology and Genetics and High Throughput Screening Resource Center, The Rockefeller University, New York, NY 10065.