NIH Study Implicates Hyperactive Immune System in Aging Brain Disorders

In a study of fruit flies, NIH scientists suggest that the body's immune system may play a critical role in the damage caused by aging brain disorders. The results are based on experiments in which the researchers altered the activity of Cdk5, a gene that preclinical studies have suggested is important for early brain development and may be involved in neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Previously, they found that altering Cdk5 sped up the genetic aging process, causing the flies to die earlier than normal and have problems with walking or flying late in life and greater signs of neurodegenerative brain damage. In this study, they suggested that altering Cdk5 resulted in the death of dopamine releasing neurons, especially in the brains of older flies. Further experiments in flies suggested the neuron loss happened because altering Cdk5 slowed autophagy, which in turn triggered the immune system to attack the animal's own neurons. Genetically restoring the waste system or blocking the immune system's responses prevented the reduction in dopamine neurons caused by altering Cdk5. The researchers concluded this chain reaction in which a breakdown in autophagy triggers a widely destructive immune reaction may occur in the human brain during several neurodegenerative disorders, and that further studies may want to look to these systems for new treatment targets and strategies.