• Semple, Bridgette D.
• Drysdale, Candace
• Sun, Mujun
• Li, Yihan
• Birchall, Ian E.
• Adlard, Paul A.
• Shultz, Sandy R.
• Alrehaili, Arwa
• Mckinley, Michael
• Doughty, Larissa
• Parker, Michael W.
• Wiley, James S.
• Ou, Wensi
• Li, Qiao-Xin
• Chen, Feng
• Wong, Joelyn
• Gu, Ben
• Masters, Colin L.
• Lim, Michael
• Park, Keunha

Abstract

<jats:title>Abstract</jats:title><jats:p><jats:bold>Background:</jats:bold> We and others have reported that glatiramer acetate promotes innate phagocytosis. <jats:bold>Methods:</jats:bold> In this study, we investigated the interaction between glatiramer acetate and amyloid-β (Aβ) by using circular dichroism and microscale thermophoresis. Glatiramer acetate was delivered intracerebroventricularly to 22-month-old APP/PS1 mice by using mini-osmotic pumps. Mice underwent behavioural testing for two consecutive weeks after three-weeks treatment. Five weeks after implantation, animals were sacrificed and brain samples were collected for electrophysiology, immunochemistry and histopathology studies. Intracerebroventricular delivery of glatiramer acetate to sheep was also examined. <jats:bold>Results:</jats:bold> Glatiramer acetate binds to amyloid-β within high affinity and antagonize its toxicity. Glatiramer acetate treatment significantly improved cognitive function, restored long-term potentiation, reduced soluble amyloid-β and amyloid-β plaques in aged APP/PS1 mice, and promoted energy metabolism in sheep. <jats:bold>Conclusions:</jats:bold> Our results suggest a novel treatment strategy that targets both innate phagocytosis and amyloid-β, which may prove useful for treatment of all stages of Alzheimer’s disease.</jats:p>

Topics

• toxicity