What is it about?

Alzheimer’s disease is the major cause of dementia. In Alzheimer’s disease, amyloid proteins begin to accumulate in the brain already before symptoms appear or progressive neuron loss occurs. Immune cells in the brain, called microglia, respond to this buildup of amyloid proteins. Changes in how microglia look can indicate their response to these proteins and inflammation. In this study, we tested the effects of blood plasma injections in rats with Alzheimer’s-like amyloid buildup. We wanted to see if the timing of the treatment mattered, so we started injections in two different groups of rats: one before the amyloid proteins clumped into plaques and one after. Each group received one of three treatments: blood from healthy exercise-trained rats, blood from healthy sedentary rats, or a control saline solution. Each treatment was administered as injections to the rats’ tail veins 2 to 3 times a week over 6 weeks. Previously, we found that blood plasma from exercise-trained rats helped form new neurons in a brain area important for memory and learning, likely because this blood had fewer molecules that cause inflammation. In this study, we wanted to see if this “exercised blood plasma” also affected inflammation and microglia in the Alzheimer’s rats' brains. First, we compared untreated Alzheimer’s rats to healthy rats. The microglia in the Alzheimer’s rats had fewer and shorter projections than those in healthy rats, suggesting a response to the amyloid buildup. We then looked at the treatment effects and found that when the Alzheimer’s rats were treated with blood plasma from exercise-trained rats at the early pre-plaque stage, their microglia showed more and longer projections, and the level of a key inflammatory molecule decreased. Despite these findings implying beneficial effects from the treatment, we did not detect changes in cognitive function. Treatment of the Alzheimer’s rats at the later disease stage did not affect microglia, amyloid plaques, or cognitive function, although it did seem to reduce the same key inflammatory molecule as in the rats treated at an earlier stage. These results highlight the importance of early timing of interventions for Alzheimer’s disease.

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Why is it important?

We explored a potential new treatment approach for Alzheimer’s disease, focusing on the use of blood plasma from exercise-trained donors to deliver the benefits of exercise to the brain. Our study provides evidence supporting the connection between exercise-induced changes in blood and brain health. It suggests that factors in the blood of exercise-trained individuals could be harnessed to develop treatments against Alzheimer’s disease progression. The findings highlight the importance of early intervention in treating Alzheimer’s disease. We found that early treatment with plasma from exercise-trained donors may positively affect microglia and reduce inflammation, which underscores the potential for early therapeutic strategies to prevent or slow disease progression.

Perspectives

Although our study was conducted on rats, it opens up the possibility of translating these findings to humans. If benefits could be similarly observed in human trials, this could pave the way for innovative treatments for Alzheimer’s disease.

Atefe Tari
Norwegian University of Science and Technology

Read the Original

This page is a summary of: Effects of Intravenously Administered Plasma from Exercise-Trained Donors on Microglia and Cytokines in a Transgenic Rat Model of Alzheimer’s Disease, Brain Plasticity, May 2024, IOS Press,
DOI: 10.3233/bpl-230154.
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