New Study Finds Changes to Blood Immune Cells in Alzheimer’s Disease

Immune genes previously associated with higher Alzheimer’s risk may also be vulnerable to changes caused by individual lifestyle factors and behaviors, according to a new BrightFocus Foundation-funded study published in Neuron. The research team hopes their findings will eventually lead to new avenues for research into therapeutic targets. 

Lead investigator David Gate, PhD, is a BrightFocus Alzheimer’s Disease Research grantee and assistant professor of neurology at Northwestern University. The research team investigated immune cells in the blood of individuals with Alzheimer’s disease.  

They found that every type of immune cell showed modifications driven by a person’s behavior or environment, called “epigenetic” changes. These occur to the packaging, or chromatin, that surrounds DNA inside a cell. The cell’s DNA can become altered when the packaging is left open—a common sign of epigenetic changes.    

Digging deeper, they uncovered that the immune cell genes most impacted by these changes are also known risk factors for Alzheimer’s disease. For example, researchers discovered a gene whose protein is thought to facilitate T-cell entry into the brain was particularly vulnerable to epigenetic changes.   

The authors point to environmental factors or viral infection as possible instigators behind the modified genes.  

“It is possible that these findings implicate the peripheral immune response in Alzheimer’s disease risk,” Dr. Gate said. “We haven’t yet untangled whether these changes are reflective of brain pathology or whether they precipitate the disease.” 

Through Alzheimer’s Disease Research funding, Dr. Gate is using postmortem brain tissue samples and sophisticated molecular tools to determine if specific immune cells, called T-cells, appear in the same places as misfolded key proteins in Alzheimer’s disease. He earned the Alzheimer’s Disease Research Distinguished Investigator Award in 2023, awarded to the top-ranked grant proposal for that year. 

Read the full story from Northwestern University.