Researchers at the Mayo Clinic have discovered specific molecular changes in the blood-brain barrier that could help improve the diagnosis and treatment of Alzheimer’s disease.
Their study, published in Nature Communications, sheds light on how the brain’s protective barrier is disrupted in Alzheimer’s and identifies potential biomarkers that may be used to detect the disease earlier.
Understanding the Blood-Brain Barrier in Alzheimer’s
The blood-brain barrier is a network of blood vessels and tissues that acts as a protective shield, preventing harmful substances in the blood from reaching the brain. In Alzheimer’s disease, this barrier becomes damaged, allowing harmful molecules to enter the brain and contribute to neurodegeneration.
However, scientists have struggled to pinpoint the exact molecular changes that lead to this dysfunction—until now.
Dr. Nilüfer Ertekin-Taner, senior author of the study and chair of the Department of Neuroscience at Mayo Clinic, emphasized the importance of these findings. “These molecular signatures have high potential to become novel biomarkers that capture brain changes in Alzheimer’s disease,” she said.
Key Findings: Molecular Disruptions in Alzheimer’s
To conduct the study, researchers analyzed brain tissue samples from 12 Alzheimer’s patients and 12 healthy individuals who had donated their brains for research. They also examined large external datasets and thousands of cells across six different brain regions, making this one of the most detailed studies on the blood-brain barrier in Alzheimer’s disease.
Their focus was on vascular cells, particularly:
- Pericytes – Cells that maintain the structural integrity of blood vessels in the brain.
- Astrocytes – Support cells that assist pericytes in regulating the blood-brain barrier.
The team discovered altered communication between pericytes and astrocytes in Alzheimer’s patients. They found that this interaction was largely influenced by two key molecules:
- VEGFA – A molecule that stimulates blood vessel growth.
- SMAD3 – A protein that plays a crucial role in regulating cell function and response to environmental changes.
How VEGFA and SMAD3 Affect the Blood-Brain Barrier
By studying cellular models and zebrafish models, the researchers confirmed that higher levels of VEGFA led to lower levels of SMAD3 in the brain. This interaction weakens blood vessel function and likely contributes to Alzheimer’s-related damage.
To further explore this connection, the scientists took stem cells from blood and skin samples of Alzheimer’s patients and healthy individuals. When they exposed these cells to VEGFA, they observed a drop in SMAD3 levels, confirming the negative impact of VEGFA on blood-brain barrier integrity.
Potential Biomarker for Alzheimer’s
The study also found that Alzheimer’s patients with higher SMAD3 levels in their blood had less vascular damage and better disease outcomes. This suggests that SMAD3 levels in the blood could serve as a potential biomarker for identifying individuals at risk of Alzheimer’s or tracking disease progression.
Next Steps in Research
The researchers now plan to:
- Investigate how SMAD3 levels in the brain correlate with SMAD3 levels in the blood to confirm its potential as a diagnostic tool.
- Explore whether targeting SMAD3 could help protect the blood-brain barrier and slow Alzheimer’s progression.
- Search for other molecules involved in maintaining blood vessel health in Alzheimer’s patients.
These findings offer new hope for detecting and treating Alzheimer’s disease by focusing on the vascular system, a previously underexplored area in neurodegenerative research. If future studies confirm these results, targeting the VEGFA-SMAD3 pathway could lead to new Alzheimer’s treatments and earlier diagnostic tests.
If you care about Alzheimer’s, please read studies about the likely cause of Alzheimer’s disease , and new non-drug treatment that could help prevent Alzheimer’s.
For more information about brain health, please see recent studies about diet that may help prevent Alzheimer’s, and results showing some dementia cases could be prevented by changing these 12 things.
The research findings can be found in Nature Communications.
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