Vascular Changes in Brain Linked to Alzheimer's Disease Uncovered by Researchers

Uncovering the Molecular Signatures of Blood-Brain Barrier Dysfunction in Alzheimer’s Disease

Alzheimer’s disease affects millions of people worldwide, and researchers have been tirelessly working to understand the mechanisms underlying this neurodegenerative disorder. One of the key findings in this area of study is the disruption of the blood-brain barrier, which plays a vital role in protecting the brain from harmful substances circulating in the blood. In a recent study, researchers at Mayo Clinic and collaborators investigated the unique molecular signatures of blood-brain barrier dysfunction, which could pave the way for new diagnostic and treatment approaches for Alzheimer’s disease.

The Study and Findings

The study was published in Nature Communications and involved analyzing human brain tissue from the Mayo Clinic Brain Bank, along with published datasets and brain tissue samples from other collaborating institutions. The cohort included brain tissue samples from 12 patients with Alzheimer’s disease and 12 healthy patients with no confirmed Alzheimer’s disease, all of whom had donated their tissue for science.

The research team analyzed thousands of cells in more than six brain regions, with a focus on brain vascular cells, which make up a small portion of cell types in the brain. They specifically looked at two cell types that play an important role in maintaining the blood-brain barrier: pericytes and their support cells known as astrocytes, to determine if and how they interact.

The research team found that patients with Alzheimer’s disease exhibited altered communication between these cells, mediated by two molecules known as VEGFA and SMAD3. Using cellular and zebrafish models, the researchers validated their finding that higher levels of VEGFA lead to lower levels of SMAD3 in the brain. The team used stem cells from blood and skin samples of Alzheimer’s disease patient donors and the control group. They treated the cells with VEGFA to see how it affected SMAD3 levels and overall vascular health.

Biomarkers for Alzheimer’s Disease

Senior author Nilüfer Ertekin-Taner, M. D., Ph. D., chair of the Department of Neuroscience at Mayo Clinic, said that the molecular signatures have high potential to become novel biomarkers that capture brain changes in Alzheimer’s disease. This means that the findings could be used to develop diagnostic tools that accurately detect the earliest stages of Alzheimer’s disease.

Potential Therapeutic Targets

The team plans to further study the SMAD3 molecule and its vascular and neurodegenerative outcomes for Alzheimer’s disease. They also aim to search for other molecules with the potential to maintain the blood-brain barrier. Understanding these molecular mechanisms is essential in uncovering new therapeutic targets to develop novel treatments for the disease.

Conclusions

The work of the Mayo Clinic researchers, in collaboration with other institutions, is an important contribution to the field of Alzheimer’s disease research. It sheds light on the role of the blood-brain barrier and its disruption in Alzheimer’s disease. The molecular signatures provide a roadmap for further research that can help identify therapeutic targets and biomarkers for early diagnosis and treatment. Further studies could lead to new avenues for novel therapies and tools to detect the earliest stages of the disease, ultimately improving the lives of people with Alzheimer’s disease and their families.

References

https://www.mayoclinic.org/medical-professionals/neurology-neurosurgery/news/blood-brain-barrier-dysfunction-may-contribute-to-alzheimers-disease/mac-20400228
https://www.nature.com/articles/s41467-021-24756-z

Originally Post From https://newsnetwork.mayoclinic.org/discussion/researchers-identify-vascular-changes-in-the-brain-linked-to-alzheimers-disease/

Vascular Changes in Brain Linked to Alzheimer’s Disease Uncovered by Researchers