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A gene responsible for compacting trash inside the brain appears to be a key player in Alzheimer's disease, and doctors may be able to target it to better treat or help prevent the devastating condition, new UVA Health research suggests.

Researchers led by John Lukens, Ph.D., investigated the function of the CASS4 gene after it was identified as an Alzheimer's risk factor in numerous studies. They found that it helps direct brain-cleaning immune cells called microglia, and when the gene's proper function was disrupted, the effects were dire: The microglia could no longer effectively respond to harmful plaques forming in the brain, and they were far less able to contain and compact the toxins that make up those plaques. That allowed the plaques to grow more quickly and spread more aggressively.

"These findings break new ground in our understanding of how this genetic risk factor contributes to Alzheimer's disease," said Lukens, director of UVA's Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases. "Our work further suggests that defective CASS4 activity may serve as an early-onset biomarker to detect Alzheimer's and that therapeutic strategies which boost its function may offer a much-needed approach to treat this devastating brain disease."

Lukens and his colleagues have published their new findings in the Journal of Experimental Medicine.

Alzheimer's affects more than 6 million Americans. It is a progressive disease that worsens over time, robbing people of their memories to the point they can forget their own children.

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