A groundbreaking study conducted by Northwestern Medicine has revealed that RNA interference may play a crucial role in the development of Alzheimer's disease. For the first time, scientists have pinpointed short strands of toxic RNAs that contribute to brain cell death and DNA damage in both Alzheimer's patients and aged brains. This finding sheds light on the mechanisms underlying neuron death and provides new avenues for potential treatment.

According to the research, older individuals with exceptional memory capacity, known as SuperAgers, have higher levels of protective short RNA strands in their brain cells. These protective strands are found to decrease as the brain ages, potentially allowing Alzheimer's to develop. This discovery suggests that the balance between toxic and protective sRNAs shifts toward the harmful ones in aging brain cells.

Marcus Peter, the Tom D. Spies Professor of Cancer Metabolism at Northwestern University Feinberg School of Medicine and the corresponding study author, expressed the significance of this finding by stating, "Nobody has ever connected the activities of RNAs to Alzheimer's. 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."

Currently, the focus of Alzheimer's drug discovery has predominantly centered on reducing amyloid plaque load in the brain and preventing tau phosphorylation or tangles. However, these approaches have yet to yield effective and well-tolerated treatments. The Northwestern study suggests a different approach, focusing on stabilizing or increasing the levels of protective short RNAs in the brain as a potential way to halt or delay Alzheimer's and neurodegeneration.

While drugs that can achieve this exist, further testing in animal models and improvement is needed. The next step in the research is to investigate the exact contribution of toxic sRNAs to the cell death observed in Alzheimer's disease. This will involve studying different animal and cellular models and analyzing brains from Alzheimer's patients. Additionally, the team aims to screen for better compounds that can selectively increase the level of protective sRNAs or block the action of the harmful ones.

To understand the role of toxic and protective short RNAs, it is essential to recognize that all our gene information is stored in DNA, which is then converted into RNA to facilitate the production of proteins. Short RNAs, a class of non-coding RNAs, play crucial regulatory roles in the cell. However, Peter and colleagues have identified specific sequences within these short RNAs that can cause cell death by blocking the production of proteins necessary for cell survival. The data suggest that these toxic sRNAs contribute to the death of neurons and the development of Alzheimer's disease.

The toxic sRNAs are normally inhibited by protective sRNAs, such as microRNAs. However, the levels of these protective sRNAs decrease with aging, allowing the harmful sRNAs to damage cells. To arrive at these conclusions, scientists analyzed various brain samples, including Alzheimer's disease mouse models, brains of young and old mice, stem cell-derived neurons, and human brain-derived neuron-like cell lines.

The Northwestern study not only sheds light on the mechanisms behind Alzheimer's disease but also presents a new potential approach to treatment. By focusing on the balance of short RNAs, researchers hope to develop interventions that can preserve brain cell integrity and delay the onset of neurodegenerative diseases.