An Israeli study shedding new light on the elusive mechanisms behind sporadic Alzheimer's Disease could pave the way for groundbreaking treatments and prevention strategies.
Alzheimer's is the most common form of dementia, suffered by more than 55 million worldwide, predominately afflicting adults 65 and older. The disorder is characterized by the progressive degeneration of nerve cells caused by an accumulation of toxic proteins in the brain, resulting in a devastating decline in cognitive function.
The most common form of the disorder is "sporadic," which accounts for about 95 percent of all cases. The exact cause of sporadic Alzheimer's disease is not well understood, but it is believed to result from a combination of genetic, environmental, and lifestyle factors.
The remaining five percent of diagnoses are "familial," meaning that Alzheimer's can be traced to a family history or genetic mutations.
The linkage between the genetic mutations and the buildup of toxic proteins in familial Alzheimer's is relatively clear, but the triggers for protein accumulation in sporadic Alzheimer's have remained enigmatic.
But researchers at the Haifa-based Technion, led by Professor Michael Glickman and Dr. Inbal Maniv, hypothesized that the protein buildup is associated with a malfunction in the ubiquitin-proteasome system, the body's mechanism for clearing away proteins. To test this theory, the research team developed a sophisticated model system of human neurons, enabling them to investigate the involvement of the ubiquitin system in Alzheimer's disease development.
The team found that damage to the ubiquitin system lead to the accumulation of toxic proteins, even in otherwise healthy tissue, replicating the hallmark pathology of Alzheimer's.
Perhaps the most promising aspect of this study lies in the development of an RNA molecule engineered to specifically silence a component of the ubiquitin system. Remarkably, treatment with this molecule was able to mitigate the disease's pathology in the experimental model. This groundbreaking finding suggests that the RNA molecule could serve as a prototype for the development of effective Alzheimer's treatments.
The Technion team, whose findings were recently published in the peer-reviewed Nature Communications journal, say their research could potentially lead to the development of drugs to screen for and treat sporadic Alzheimer's. (ANI/TPS)
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