Genetic Risk Factors for Neurodegenerative Disease Tied to Immune Cell Function

Proinflammatory processes have been implicated in disease progression in ALS, but how genetic risk factors for ALS affect immune system function is largely unknown. A recent study published online May 2 in Science from the groups of Christope Benoist at Harvard Medical School, Barbara Stranger at University of Chicago and Philip de Jager at the Brigham and Women’s Hospital, together with colleagues from the Broad Institute, Stanford and Massachusetts General Hospital, presents an extensive analysis of the relationship between gene expression changes in the adaptive and innate immune system and genetic risk factors of disease.

The researchers, led by postdoctoral scholar Towfique Raj, analyzed expression of >19,000 genes in T cells and monocytes (adaptive and innate immune cells, respectively) from a multi-ethnic cohort of 461 healthy, young individuals, and cross-referenced the genomic data from these cells with genetic risk factors for diseases. They found that risk factors for autoimmune disease are associated with changes in T-cell gene expression, whereas high risk genetic variants for Alzheimer’s and Parkinson’s diseases are more tightly related to changes in monocyte function. These finding provide new insight into how genetic variation contributes to changes in innate immune system function, and uncovers new targets for potentially attenuating development of these neurodegenerative diseases.

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