Alzheimer’s disease, projected to impact approximately 6.7 million individuals in the U.S. by 2023, leads to significant brain cell loss. However, the mechanisms triggering neuron death have been poorly understood. A groundbreaking study from Northwestern Medicine now suggests that RNA interference may play a crucial role in the development of Alzheimer’s. For the first time, scientists have pinpointed short strands of toxic RNAs contributing to brain cell death and DNA damage in both Alzheimer’s and aging brains. The researchers note a decline in protective short RNA strands during aging, potentially creating conditions conducive to Alzheimer’s progression.
The study also uncovers that older individuals exhibiting superior memory capacity, known as SuperAgers (aged 80 and older with memory comparable to individuals 20 to 30 years younger), have higher levels of protective short RNA strands in their brain cells. Marcus Peter, the corresponding study author, emphasizes the unprecedented connection between RNA activities and Alzheimer’s, revealing a shift towards toxic RNAs in aging brain cells.
Published in Nature Communications, this Northwestern discovery may extend beyond Alzheimer’s, providing a new explanation for the gradual onset of neurodegenerative diseases as cells lose protection with age. The findings suggest a novel avenue for treatment, proposing that stabilizing or increasing protective short RNAs in the brain could offer a fresh approach to halt or delay Alzheimer’s and neurodegeneration.
Contrary to conventional drug discovery efforts focused on reducing amyloid plaque load and preventing tau phosphorylation, the study advocates for exploring the potential of enhancing protective short RNAs. While such drugs exist, further testing and improvements are needed. Marcus Peter envisions the next phase of research involving the examination of different animal and cellular models, as well as brains from Alzheimer’s patients, to ascertain the exact role of toxic short RNAs in cell death and screen for compounds that selectively increase protective short RNAs or block the action of toxic ones.
The study sheds light on the significance of short RNAs, both toxic and protective, in the context of gene information storage and processing. As essential players in cellular functions, short RNAs, particularly microRNAs, act as guards against toxic RNAs, preventing their entry into cellular machinery. However, the decline in the number of these guards with aging allows toxic RNAs to damage cells, contributing to Alzheimer’s development. The research involved the analysis of various models, including Alzheimer’s disease mouse models, young and old mice, induced pluripotent stem cell-derived neurons, and brains from individuals with SuperAger memory capacity, among others.
