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Scientists Discover New Gene That Increases Alzheimer's Disease Risk

BEC CREW
7 OCT 2015

An immune system gene that’s associated with a higher risk of Alzheimer’s disease has been identified by researchers in the US. Older adults and Alzheimer's patients who are carrying a specific variant of the IL1RAP gene were found to have higher rates of amyloid plaque accumulation in the brain, which is one of the key drivers of the disease.

 

Not only could the discovery lead to quicker diagnoses and better identification of at-risk patients, but researchers suggest that by manipulating the IL1RAP immune pathway they could figure out how to either slow the progression of the disease, or perhaps stop it altogether.

"These findings suggest that targeting the IL1RAP immune pathway may be a viable approach for promoting the clearance of amyloid deposits and fighting an important cause of progression in Alzheimer's disease," said one of the team, Andrew Saykin from the Indiana University School of Medicine.

Previous research has linked another genetic factor to the development of Alzheimer's disease - the APOE e4 allele. But when Saykin and his team imaged the brains of almost 500 volunteers via PET (positron emission tomography) scans, and assessed the levels of brain amyloid deposits at the time and then two years later, they found that the IL1RAP variant had an even stronger effect on the progression of the disease than APOE e4.

The gene IL1RAP codes for an immune signalling factor called the Interleukin-1 Receptor Accessory Protein, which triggers the production of pro-inflammatory proteins in response to infection, tissue damage, or stress. It also influences the activity of the microglia - a specific type of cell found in the brain and the spinal cord that acts as the first and main line of immune defence in the central nervous system.

The study, published in the journal Brain, found that over the two-year period, people carrying the IL1RAP variant had a lower level of microglial activity, which means the brain is less able to clear out protein build-up; a faster degeneration of the temporal cortex, which is the region of the brain involved with memory; and faster cognitive decline. 

"This was an intriguing finding because IL1RAP is known to play a central role in the activity of microglia, the immune system cells that act as the brain's 'garbage disposal system' and the focus of heavy investigation in a variety of neurodegenerative diseases," said one of the researchers, Vijay K. Ramanan.

Regardless of whether a patient has APOE e4 too, the presence of the IL1RAP variant was associated with an overall greater likelihood of progression from mild cognitive impairment to Alzheimer's disease.

But there is good news. The researchers think that treatments specifically targeting the IL1RAP immune pathway could increase the brain's ability to clear out amyloid deposits in patients carrying the gene variant. And fortunately, drugs that target the so-called IL-1/IL1RAP pathway already exist for the treatment of various inflammatory conditions, which means clinical testing could be right around the corner.

"These findings suggest that targeting the IL1RAP immune pathway may be a viable approach for promoting the clearance of amyloid deposits and fighting an important cause of progression in Alzheimer's disease," said Saykin.