|IU's Dr. Vijay Ramanan|
There are a variety of theories as to why people develop Alzheimer's. And one of the best known is that toxic clusters of amyloid beta in the brain wipe out memories and trigger dementia in the elderly.
Now researchers at Indiana University say that they have determined that the IL1RAP immune pathway could provide a promising avenue for drug developers. And they're quick to add that some experimental therapies that already hit this target could offer a quick way to help determine their utility against Alzheimer's.
The team confirmed an observation that has been made before: the APOE e4 allele is associated with a significant accumulation of amyloid beta. But they were surprised to find that the IL1RAP gene--which they note codes for the immune signaling factor interleukin-1 receptor accessory protein--"showed an independent and even stronger influence on amyloid accumulation."
They also determined that the gene was linked to a lower level of microglial activity as measured by PET scans; increased atrophy of the temporal cortex; swift cognitive decline and a "greater likelihood among study participants of progression from mild cognitive impairment to Alzheimer's disease."
"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 Dr. Vijay Ramanan, postdoctoral researcher at the IU School of Medicine.
There are already experimental anti-inflammatories and antibodies that are designed to hit this target, offering a shortcut in determining the impact on patients.
"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 Andrew Saykin, director of the Indiana Alzheimer Disease Center and the national Alzheimer's Disease Neuroimaging Initiative Genetics Core.
It's also useful to note that while many researchers believe that amyloid beta causes Alzheimer's, there's no consensus at the FDA on that point. And while many programs have been put in place to treat the disease, the vast majority have failed in the clinic, including drugs that aim at amyloid beta clearance.
- here's the release