IL1RAP variant

A New Target to Slow Alzheimer Disease?

Alan R. Jacobs, MD

Researchers led by scientists at the Indiana University School of Medicine have discovered an immune system gene associated with higher rates of amyloid accumulation in patients with Alzheimer disease and in older adults at risk for Alzheimer disease.

Five hundred subjects underwent amyloid PET scan imaging at baseline, and again after 2 years. A genome-wide analysis then identified genetic variance associated with the rate of plaque accumulation over the 2-year window.

In addition to finding the expected APOE e4 gene variant, the investigators also found IL1RAP—a gene coding for the immune signal interleukin-1 receptor accessory protein—which showed an independent and even stronger influence on amyloid accumulation.

A variant of IL1RAP was associated with lower levels of microglial activity, greater atrophy of the temporal cortex, faster cognitive decline, and increased rate of progression from mild cognitive impairment to Alzheimer disease.

The researchers conclude that targeting the IL1RAP pathway may be a viable approach to clearing amyloid from the brain and slowing the progression of Alzheimer disease.