The causes of Alzheimer’s are not completely known, although the disease has been related to the accumulation of amyloid beta proteins in the brain and the presence of the APOE4 gene – carried by almost half of the patients – however, in the appearance This dementia could also influence the way our genes are expressed based on their interactions with the environment and lifestyle, known as epigenetics.
Now, Northwestern Medicine scientists have found altered immune genes in the blood of Alzheimer’s patients, many of which increase a person’s risk of developing the disease. This means that the immune system in the blood of Alzheimer’s patients is epigenetically altered and that the habits or environment of these people have caused changes that influence the way their genes work.
The authors of the study point out that the cause of this could be a previous viral infection, environmental pollutants, or other lifestyle factors and behaviors. “These findings may implicate the peripheral immune response in the risk of Alzheimer’s disease,” said lead researcher David Gate, an assistant professor of neurology at Northwestern University Feinberg School of Medicine. “We have not yet clarified whether these changes reflect brain pathology, or whether they precipitate the disease.”
Epigenetic changes that may predispose to Alzheimer’s
Previous research has shown that many of the mutated genes that put a person at greater risk for Alzheimer’s are in the immune system. But scientists primarily studied the brain’s central immune system because Alzheimer’s is a brain disease, and so they have largely ignored the immune system in the blood, also known as the peripheral immune system.
Gate decided to study blood and discovered, together with his colleagues, that each type of immune cell in Alzheimer’s patients has epigenetic changes, indicated by open chromatin. Chromatin is the packaging of DNA within cells. When chromatin is open (or exposed), the cells’ genome is vulnerable to alterations.
Gate then examined which genes are most open in these immune cells, that is, most exposed. He discovered that a receptor, CXCR3, on T cells was more exposed. Gate believes that CXCR3 functions as an antenna on T cells that allows them to enter the brain. T cells do not normally enter the brain because they can cause inflammation.
“It could be that environmental factors, such as pollutants or infections that a person has throughout their life, cause the epigenetic changes observed in patients with Alzheimer’s”
“The brain gives off a signal that it is damaged, and T cells target that signal through their antenna, CXCR3,” Gate said, adding: “T cells can be very toxic in the brain, but we also don’t know. whether these cells could be trying to repair damage in the brain.”
Gate also discovered epigenetic changes in inflammatory proteins in white blood cells called monocytes. “Taken together, these findings indicate that immune function in Alzheimer’s patients is significantly altered,” Gate said. “It could be that environmental factors, such as pollutants or infections that a person has throughout their life, cause these epigenetic changes.”
The findings have been published in Neuron and have identified several genes that may be therapeutic targets to manipulate the peripheral immune system. Researchers now plan to conduct preclinical studies using in vitro culture systems and animal models to test these targets.
