Brain Vascular Changes Linked to Alzheimer’s Disease: Study

Brain Vascular Changes Linked to Alzheimer's Disease: Study

The Blood-Brain Barrier in Alzheimer’s Disease: Molecular Markers for Diagnosis and Treatment

The blood-brain barrier (BBB) is a complex network of blood vessels and tissues that protects and nourishes the brain while shielding it from harmful substances in the bloodstream. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions worldwide and is characterized by the accumulation of toxic proteins in the brain, leading to cognitive decline and other symptoms. The BBB has been implicated in the pathogenesis of AD, and researchers at the Mayo Clinic and collaborating institutions have identified molecular markers of BBB disruption that may pave the way for new diagnostic and therapeutic strategies.

The Study

The research team analyzed human brain tissue samples from the Mayo Clinic Brain Bank and other sources to identify distinct molecular signatures of BBB dysfunction in AD. The study cohort consisted of brain tissue samples from 12 AD patients and 12 healthy controls who donated their tissue for science. By analyzing thousands of cells in more than six brain regions, the researchers focused on brain vascular cells, which make up a small portion of cell types in the brain, to examine molecular changes associated with AD.

The Role of Pericytes and Astrocytes

The team looked specifically at two cell types that play crucial roles in maintaining the integrity of the BBB: pericytes and their support cells known as astrocytes. The researchers found that AD patients’ brain tissue samples exhibited altered communication between these two cell types, mediated by two key molecules: VEGFA and SMAD3.

VEGFA and SMAD3

VEGFA (vascular endothelial growth factor A) stimulates the growth of blood vessels, while SMAD3 plays a crucial role in cellular responses to the external environment. The team found that increased levels of VEGFA lead to lower levels of SMAD3 in the brain, indicating an interaction between these molecules in AD pathogenesis.

The Validation

To validate their findings, the team used cellular and zebrafish models to analyze the effects of VEGFA on SMAD3 levels and overall vascular health. They found that treatment with VEGFA caused a decline in SMAD3 levels in brain pericytes, confirming an interaction between these molecules and their role in BBB dysfunction in AD.

The Implications

These molecular markers of BBB disruption in AD have high potential to become novel biomarkers that capture brain changes in AD. Donors with higher blood SMAD3 levels had less vascular damage and better AD-related outcomes. Hence, developing more specific diagnostic and therapeutic tools targeting the interaction between VEGFA and SMAD3 could lead to more precise and effective treatments for AD.

Conclusion

The study by the Mayo Clinic researchers and associates provides new insights into the complex role of the BBB in AD pathogenesis. By identifying distinct molecular markers of BBB disruption, the study points towards new avenues for diagnosis and treatment of this devastating disease. Developing more specific diagnostic tools and therapeutic strategies targeting the VEGFA-SMAD3 interaction will likely improve outcomes for patients with AD. It underscores the importance of further research into the molecular mechanisms of BBB dysfunction in AD and may bring us closer to finding a cure for this debilitating disorder.

Originally Post From https://zeenews.india.com/health/study-links-brain-vascular-changes-to-alzheimers-disease-2761472

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