Researchers from Safra Center for Neuroscience and the Institute for Life Sciences at Hebrew University published a study in Alzheimer's & Dementia: The Journal of the Alzheimer's Association uncovering a molecular mechanism that leads to accelerated cognitive deterioration in females living with Alzheimer’s.
Alzheimer's disease is a severe degenerative condition serving as the leading cause of dementia. The disease disproportionately affects women, characterized by a faster rate of progression and more pronounced cognitive deterioration than men. Current therapeutic protocols only aim to delay symptoms progression but are known to result in more severe side effects in women. Consequently, the decline in cognitive functioning in women with Alzheimer’s continues despite treatment, further exacerbating the challenges they face.
The study, led by brain gene expert Professor Hermona Soreq and Professor Yonatan Loewenstein, discovered a direct link between a family of mitochondrial-originated RNA fragments and the rate of dementia progression in women. The findings indicate that independent of structural brain changes, severe depletion of mitochondrial RNA fragments inherited from the mother, in the affected brain nuclei, correlates with the rapid deterioration of cognitive abilities in women with Alzheimer's.
Professor Soreq explained, "Our research presents a significant contribution to the existing body of Alzheimer’s research by uncovering new insights into the factors driving accelerated cognitive decline in women, underscoring crucial distinctions not only in disease progression but also in treatment response. Moreover, these findings have implications for treating these symptoms by RNA-based therapies, which emerged in recent years, and now present a viable option."
The study received support from the US National Institutes of Health and the Israel Science Foundation support for Basic Research and Precision Medicine. Additional members of the research team include computational biology master student, Dana Shulman and collaboration with American colleagues. These include David Bennett, Director of the Rush Alzheimer’s Disease Center and Professor of Neurological Sciences at Rush University, Professor Elliott Mufson, Director of the Alzheimer’s and Brain Trauma Research Laboratory, Barrow Neurological Institute, and Professor Sudha Seshadri, Founding Director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disease and physician at UT Health San Antonio. The study also received direct contributions from Ken Stein and Sami Segol.
"This discovery provides the first molecular explanation for the accelerated cognitive damages occurring in the brains of women with Alzheimer's disease, opening the door for improvement of current treatment protocols,” concludes Professor Soreq. “With this discovery we can take a crucial step forward in developing drugs suitable for women suffering from this devastating condition, and pave the way for optimal care and support for Alzheimer's patients and their families."