Researchers at Washington University School of Medicine have received a significant $7.5 million grant from the National Institutes of Health (NIH) to explore the mechanisms behind dementia caused by cerebral small vessel disease (CSVD). This condition is the second-leading cause of dementia in the U.S., following Alzheimer’s disease.
The funding supports the Vascular Contributions to Cognitive Impairment and Dementia (VCID) Center, part of the NIH’s “Center Without Walls” initiative. This collaboration will bring together researchers from six institutions across the country to study the impact of CSVD on brain function and cognition.
A New Approach to Understanding CSVD
The Washington University team, led by co-investigators Jin-Moo Lee, MD, PhD, Carlos Cruchaga, PhD, and Manu Goyal, MD, will apply cutting-edge imaging and multi-omic technologies to analyze cerebrospinal fluid and brain tissue. Their goal is to map out the genetic, protein, and metabolic changes in brain cells affected by CSVD, which could lead to early biomarkers for diagnosis and potential therapeutic targets.
“Through this research, we hope to pinpoint proteins that could serve as both diagnostic markers and potential drug targets,” said Dr. Lee, a neurologist and head of the Department of Neurology at Washington University.
The team will also use advanced MRI processing techniques to detect specific brain abnormalities associated with CSVD, including white matter hyperintensities—bright spots that appear on brain scans. These abnormalities are indicative of brain regions where blood flow has been compromised due to small vessel damage, leading to a range of cognitive and physical impairments.
Uncovering the Root Causes of CSVD
Cerebral small vessel disease is caused by damage to the small blood vessels in the brain, which leads to a loss of their ability to adjust blood flow as needed. Over time, this results in ischemia (reduced blood flow), which harms the brain’s white matter and contributes to symptoms of vascular dementia such as memory loss, difficulty walking, and depression.
High blood pressure and diabetes are common risk factors for CSVD, as they can lead to arteriolosclerosis (thickening of the small vessel walls) and cerebral amyloid angiopathy (CAA), a condition also linked to Alzheimer’s disease. These conditions disrupt blood flow in the brain and cause visible changes on MRI scans, such as the aforementioned white matter hyperintensities.
A New Vision for Targeted Therapies
To better understand CSVD, the research team is using a new approach to study how white matter hyperintensities develop. Traditionally, researchers have examined the brain as a whole, missing the specific changes that occur at the cellular level. The Washington University team, however, will perform detailed analyses of brain cells, using a technique called spatial transcriptomics to map out gene expression changes in specific areas of the brain.
“Our approach will allow us to pinpoint the precise genetic and cellular changes occurring in white matter hyperintensities,” said Dr. Cruchaga, a professor of psychiatry at Washington University. “By studying these changes in depth, we aim to identify novel biomarkers and therapeutic targets that could help mitigate or even reverse the damage caused by CSVD.”
Dr. Goyal, an associate professor of radiology, added that while small vessel disease is commonly seen in older patients, the exact mechanisms behind it remain poorly understood. “This grant will allow us to investigate the molecular underpinnings of CSVD with unprecedented detail,” he said. “Understanding these processes is key to developing effective treatments.”
Collaborative Effort to Advance Research
The research will be conducted with the help of patients from the Knight Alzheimer’s Disease Research Center (Knight-ADRC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). These patient cohorts will provide tissue and cerebrospinal fluid samples, allowing the team to link molecular and genetic data to clinical symptoms and MRI findings.
The NIH grant supporting this work is part of a broader effort to enhance research into dementia and cognitive decline, with the ultimate goal of improving diagnosis, treatment, and prevention strategies.
Supporting the Future of Dementia Research
This project is supported by the NIH under award number 1RF1NS139970-01. The content of this research is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH.
For more information about the VCID Center and its work on cerebral small vessel disease, visit the Washington University School of Medicine website.
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