New research using mouse models shows that targeting immune cells in the brain can be a potential avenue for Alzheimer's treatment.
The primary job of microglia is to protect the brain, but they can carry a particular gene that has been linked to an increased risk of Alzheimer's. The researchers were able to establish the nature of that genetic abnormality.
The team was able to reverse some of the inflammatory effects and synaptic toxicity that are usually seen as Alzheimer's disease progresses in the brain by blocking off the effects of the mutation.
Microglia are the brain's protectors, but can be detrimental in disease conditions.
"Our goal is to identify how they become toxic and contribute to Alzheimer's disease and whether we can identify immune modulators to reverse the toxicity without diminishing their normal protective function."
The team focused on the TREM2 gene because it is the one that signals through the AKT to modify inflammation and metabolism. The researchers used a genetic strain combining the TREM2 and the other one known to produce clumps of the Alzheimer's related tau protein in their mouse models.
The mice with the strain had memory problems, while the microglia in their brains had high levels of inflammatory molecules. The effects were similar to those seen in Alzheimer's patients.
The inflammation and damage was reversed when the drug was used. If it is found to show promise in Alzheimer's research, it shouldn't take as long as usual to be developed further, since it is already being assessed by safety agencies as a potential anti-cancer drug.
The findings support further study of this compound as a potential therapy for Alzheimer's disease.
(Li Gan)
Each dot in the image represents a different cell state. There is a cluster of disease-associated microglia on the left side.
Many of the genetic variations that are associated with an increased risk of Alzheimer's disease are expressed in the cells of the immune system, suggesting that alterations to these cells are somehow linked to the progress of the condition.
It's difficult to research Alzheimer's because we don't know what causes it or how it starts, but we can look for clues as the disease progresses.
It's encouraging to know that progress is being made in the fight against Alzheimer's, and that it will lead to better treatments one day.
A small molecule compound that has been tested in patients with cancer, readily enters the brain, potently modulates the brain's immune responses, and protects against synaptic loss in animal models of Alzheimer's disease, was identified. Let's hope this isn't the last we hear of it.
The research has been published.
