A groundbreaking research effort led by Geneva University Hospitals (HUG) and the University of Geneva (UNIGE) has provided fresh insights into age-related dementias, particularly vascular dementia – the second most common form after Alzheimer’s disease.
The study spotlights the pivotal role of the brain molecule known as chemokine receptor 5 (CCR5) in the neuronal deterioration witnessed during the development of vascular dementia.
This discovery presents hopeful avenues for prevention, enabling early identification of individuals at risk and the implementation of appropriate measures. The findings have been published in the journal Alzheimer’s and Dementia.
Vascular dementia, a subset of dementia conditions, primarily afflicts the elderly, impacting between 1% and 4% of individuals aged over 65, according to Alzheimer’s Switzerland. It results from vascular lesions that disrupt blood supply to the brain, leading to neuronal death.
Currently, there is no cure for vascular dementia, and prevention chiefly involves managing risk factors like high blood pressure, high cholesterol, diabetes, and smoking. The quest for improved preventive measures takes a significant step forward with the revelation of new disease biomarkers, such as the CCR5 receptor, which enhances the identification of those susceptible to vascular dementia.
A Novel Biomarker Unveiled The study’s focal point was CCR5, a receptor protein associated with chemokines, the immune system’s messengers. The research was led by Dr. Dina Zekry, Head of the division of Internal Medicine for the Aged at HUG and Associate Professor in the Department of Rehabilitation and Geriatrics at UNIGE’s Faculty of Medicine, in collaboration with Dr. Karl-Heinz Krause’s team.
Dr. Krause is a senior physician in the Department of Diagnostics and Medicine at HUG and Full Professor in the Department of Pathology and Immunology at UNIGE’s Faculty of Medicine, both of whom played pivotal roles in the study. Their investigation uncovered CCR5’s vital role in the response of brain cells to oxidative stress, a mechanism intricately linked to neuronal demise. Additionally, they identified a connection between a specific genetic variant of CCR5 and apolipoprotein E (ApoE), a known player in age-related dementia.
This intricate genetic interplay significantly amplifies the risk of vascular dementia. As Dr. Benjamin Tournier, the study’s first author, points out, “Individuals over the age of 80 with this specific genotype are eleven times more likely to develop vascular dementia.”
This research, characterized by its translational nature, translating fundamental discoveries into concrete clinical applications, has contributed to a better understanding of dementia mechanisms through a series of experiments.
The study began by illuminating CCR5’s potential role in ischemic mechanisms through in-vitro examinations of mouse neurons. Subsequently, genetic variations in the CCR5 and ApoE genes were scrutinized in a cohort of 362 participants, with their findings verified in an Italian cohort, further solidifying the discovery’s robustness.
A Major Leap Toward Prevention and Treatment Professor Zekry underscores the significance of this discovery as a new target for comprehending and addressing age-related dementia. She states, “This is a major advance that opens doors for the early identification of individuals at risk and for the development of targeted therapies. It offers considerable hope for our society with regard to neurocognitive diseases as a whole.”
The findings not only lay the groundwork for early risk identification but also hold the potential to spawn fresh treatment strategies, aimed at enhancing the quality of life and functionality of those affected.