May 11, 2023 – Hebrew University of Jerusalem (HU) researchers discovered a molecular mechanism that leads to accelerated cognitive deterioration in women with Alzheimer’s disease. 

Profs. Hermona Soreq and Yonatan Loewenstein of the Hebrew University Edmond & Lily Safra Center for Brain Sciences led the study that was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.  

The researchers 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 in affected brain nuclei that have been inherited from the patient’s mother correlate with the rapid cognitive deterioration.  

“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,” Prof. Soreq says. “We can now 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.”  

Alzheimer’s disease is a severe degenerative condition that is the leading cause of dementia. The disease disproportionately affects women in both a faster progression rate and more pronounced cognitive deterioration compared to men. Current therapeutic protocols only delay the progression of symptoms but also cause more severe side effects in women, further exacerbating the challenges they face.  

“Our research provides new insights into factors driving the accelerated cognitive decline in women, underscoring crucial distinctions not only in disease progression but also in treatment response, which is a significant contribution to the body of Alzheimer’s research,” says Prof. Soreq. “Moreover, these findings have implications for treating these symptoms with RNA-based therapies, which now present a viable option.” 

Additional members of the research team include computational biology master’s student, Dana Shulman. American team members include David Bennett, Director of the Rush Alzheimer’s Disease Center, and Professor of Neurological Sciences at Rush University; Prof. 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 received support from the U.S. National Institutes of Health and the Israel Science Foundation support for Basic Research and Precision Medicine.