Research from the University of Southampton (UK) has found that blocking a receptor in the brain responsible for the regulation of immune cells could provide protection against the behavior and memory changes seen in Alzheimer’s disease.
It was previously believed that Alzheimer’s disease disturbs the brain’s immune response, but this novel research adds to a growing body of work indicating that inflammation can drive the development of the disease. These findings suggest that a reduction in inflammation could slow or halt progression of the disease.
The team used tissue samples from brains of the same age, some healthy and others with Alzheimer’s. They then counted the numbers of microglia, an immune cell, in the samples and found that these were more numerous in brains with Alzheimer’s disease. They also discovered that the activity of the molecules regulating the microglia correlated with the severity of the disease.
The researchers then studied the microglia in mice models, which had been bred to develop features of Alzheimer’s, in order to determine if blocking the receptor responsible for their regulation would improve cognitive skills. They gave the mice oral doses of an inhibitor known to block CSF1R, the microglia regulating receptor, and found that the treatment could prevent the rise of microglia numbers seen in untreated mice where the disease had progressed. The inhibitor prevented loss of communication points between the nerve cells in the brain associated with Alzheimer’s, and mice treated with it demonstrated fewer memory and behavioral problems than untreated mice.
The team also found that the healthy number of microglia needed in the brain was maintained during treatment, which suggests that blocking CSF1R only reduces excess microglia, and would not damage normal immune function.
However, the study did not find a correlated reduction of the number of amyloid plaques in the brain, which is a characteristic feature of Alzheimer’s disease. This result supports previous evidence that other factors play a more critical role in cognitive decline.
Diego Gomez-Nicola, lead author of the study, explained, “These findings are as close to evidence as we can get to show that this particular pathway is active in the development of Alzheimer’s disease.” He concluded: “The next step is to work closely with our partners in industry to find a safe and suitable drug that can be tested to see if it works in humans.”
The researchers hope that their discovery will someday lead to an effective treatment for the disease, for which there is no cure.