Young blood plasma reduces Alzheimer's disease-like brain pathologies and ameliorates cognitive impairment in 3×Tg-AD mice

Abstract

Background: Recent studies indicated that circulatory factors in blood plasma from young animals can reactivate neurogenesis, restore synaptic plasticity, and improve cognitive function in aged animals. Here, we investigated if young plasma could have a possible therapeutic effect for treatment of Alzheimer's disease (AD)-like pathologies and cognitive impairment in triple-transgenic AD (3×Tg-AD) mice. Methods: We intravenously injected plasma from 2- to 3-month-old C57BL/6 J wild-type mice into 16-17-month-old 3×Tg-AD mice twice a week for 8 weeks. The behavioral tests including open field, novel object recognition, Morris water maze, and reversal Morris water maze were conducted after 4-week plasma injections. The effect of young plasma on tau and Aβ pathologies and on the levels of synaptic proteins and neuroinflammation were assessed by Western blots and immunohistochemical staining. Results: Young plasma treatment improved short-term memory in the novel object recognition test and enhanced the spatial learning and memory in Morris water maze test and reversal Morris water maze test. Biochemical studies revealed that young plasma treatment reduced both tau and Aβ pathologies, as well as neuroinflammation in the mouse brain. However, we did not detect any significant changes in levels of synaptic proteins or the dentate gyrus neurogenesis in the mouse brain after the treatment with young plasma. Conclusions: These data indicate that young blood plasma not only ameliorates tau and Aβ pathologies but also enhances the cognitive function in 3×Tg-AD mice. These findings suggest that transfusion with young blood plasma could be a potentially effective treatment for AD.