Abigail Klein Leichman
May 15, 2023

A molecular mechanism that leads to accelerated cognitive deterioration in females with Alzheimer’s disease was described for the first time by neuroscience researchers from the Hebrew University of Jerusalem in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Alzheimer’s, the leading cause of dementia, disproportionately affects women, in whom the disease progresses faster than in men. What’s more, current therapeutic drugs to delay symptom progression cause more severe side effects in women.

The study, led by brain gene expert Prof. Hermona Soreq and Prof. 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 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.

New clue to understanding Alzheimer’s progression in women
Prof. Hermona Soreq. Photo by Yosef Adest/Hebrew University

“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,” said Soreq.

She said the study has implications for the viability of treating Alzheimer’s symptoms with RNA-based therapies that have emerged in recent years.

“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.”

The study received support from the US National Institutes of Health and the Israel Science Foundation, among others.

Additional members of the research team included HUJ computational biology master’s student Dana Shulman and American colleagues David Bennett, director of the Rush Alzheimer’s Disease Center; Prof. Elliott Mufson, director of the Alzheimer’s and Brain Trauma Research Laboratory, Barrow Neurological Institute; and Prof. Sudha Seshadri, founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Disease at UT Health San Antonio.

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