As people age, cognitive dysfunction known as dementia becomes more likely. Alzheimer's disease is the most common cause of dementia. Scientists are still working to determine the cause of Alzheimer's disease. It seems to be related to aberrant proteins in the brain known as amyloid plaques, but research has not deciphered whether these are the cause of the disorder. Other research has shown that genetics (like the APOEe4 gene variant), factors in the environment, or lifestyle choices like nutrition or activity may play a role.
Aging is a primary risk factor for Alzheimer's disease, and estimates have suggested that as many as one-third of people over the age of 85 could have Alzheimer's. New research has suggested that short RNA (sRNA) molecules are related to the disease.
A programmed cell death pathway called Death Induced by Survival gene Elimination (DISE) is triggered by certain sRNAs. These sRNAs can take on a protective or toxic form, which is determined based on the chemical structure of the sRNA. The investigators analyzed these sRNAs in several model systems, including Alzheimer's animal models; young or old mouse brains; cell cultures that had been derived from cells from Alzheimer's patients; and the brains of healthy people.
The researchers found that during aging, the level of these protective sRNAs drops, increasing the activity of the DISE cell death pathway, raising the likelihood of Alzheimer's. In people who are over the age of 80 and who have an excellent memory, so-called super-agers, these sRNAs were more likely to be found in a nontoxic, protective form. The findings have been reported in Nature Communications.
A cell culture model was also engineered to generate low levels of protective sRNAs. When these cells were exposed to protective sRNA molecules, there was a reduction in the cell death that would normally be triggered by the presence of amyloid fibers.
“Nobody has ever connected the activities of RNAs to Alzheimer’s,” said corresponding study author Marcus Peter, PhD, a Professor at Northwestern University. “Our data provide a new explanation for why, in almost all neurodegenerative diseases, affected individuals have decades of symptom-free life and then the disease starts to set in gradually as cells lose their protection with age.”
Amyloid beta plaques are a well-known hallmark of Alzheimer's disease. Unfortunately, drugs that have targeted these plaques have not yet been effective at treating Alzheimer's. Other drugs have taken aim at a different protein problem in Alzheimer's known as tau phosphorylation, but so far these drugs have not been well-tolerated and effective, noted Peter.
This study has suggested a new approach might work, however. Researchers could raise the levels of protective sRNAs. This might be a way to treat neurodgeneration in general, Peter suggested. A lot more work will be needed to determine if that is true, however.
Sources: Northwestern University, Nature Communications
