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Gene risk factors for age-related brain disorders may affect immune system function

Scientists have discovered gene variants that affect the function of immune cells in young, healthy people. Interestingly, many of these same gene variants are known risk factors for diseases that occur later in life, including Alzheimer’s and Parkinson’s. This linking of known gene risk factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into Alzheimer’s and other disorders and may one day lead to promising therapies.

Funded in part by NIH, a study by researchers at Brigham and Women’s Hospital, Boston, and colleagues appeared May 2, 2014 in Science. The work of lead author Dr. Towfique Raj was supported by an NIH Ruth L. Kirschstein National Research Service Award. This program helps ensure a diverse pool of highly trained scientists are available in appropriate scientific disciplines to address the Nation's biomedical, behavioral, and clinical research needs.

The researchers studied T-cells and monocytes, two types of immune cells in blood samples donated by 461 young, healthy volunteers of diverse ancestry living in Boston. They profiled the cells to measure the expression of more than 19,000 genes found in each cell type. They then identified how gene variants in the samples influenced the function of the immune cells.

They found that gene variants that confer risk for certain diseases, such as type 1 diabetes, also controlled the activity of T-cells. T-cells are specialized in that they adapt to environmental triggers and can respond to specific allergens and viruses. In contrast, known gene risk factors for Alzheimer’s and Parkinson’s diseases influenced the function of monocytes. Monocytes are associated with innate immunity and are more generalized in their function to fight infections and help clear away dead cells and cellular debris.

While more research is needed, the study advances our understanding of the complex interplay between disease-related genetic variations and the immune system. For the Alzheimer’s research community, the findings offer an intriguing possibility of developing interventions that enlist immune cells in delaying or preventing the onset of the disease.

Reference: Towfique R, et al. Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes. Science. May 2, 2014. doi:10.1126/science.1249547