Mayo Clinic Scientists Discover Molecular Changes in Blood-Brain Barrier Linked to Alzheimer's Disease

Researchers at Mayo Clinic have made a significant breakthrough in the diagnosis and treatment of Alzheimer's disease. By conducting extensive tissue analysis and cellular studies, they have identified unique molecular changes in the blood-brain barrier associated with the disease. This finding opens up new avenues for diagnosis and potential therapeutic approaches.

The blood-brain barrier is a complex network of blood vessels and tissues that protect the brain from harmful substances in the bloodstream. In Alzheimer's disease, this barrier becomes disrupted, leading to detrimental consequences. The researchers at Mayo Clinic, along with their collaborators, delved into the molecular signatures of this dysfunction to gain insight into the disease.

Using human brain tissue samples from the Mayo Clinic Brain Bank, as well as data from other research institutions, the team conducted a comprehensive analysis. This study included brain tissue samples from both Alzheimer's disease patients and healthy individuals who had generously donated their tissue for scientific research. The researchers examined thousands of cells across six brain regions, making this one of the most rigorous studies of the blood-brain barrier in Alzheimer's disease to date.

The researchers specifically focused on two types of brain vascular cells: pericytes and astrocytes. Pericytes are responsible for maintaining the integrity of blood vessels in the brain, while astrocytes provide support to these cells. They discovered an altered communication between these cells in Alzheimer's disease patients, which was mediated by two molecules called VEGFA and SMAD3.

Further experiments using cellular and zebrafish models confirmed that increased levels of VEGFA led to decreased levels of SMAD3 in the brain. Stem cells derived from blood and skin samples of Alzheimer's patients and control subjects were treated with VEGFA to examine its effects on SMAD3 levels and overall vascular health. The results indicated a decline in SMAD3 levels in pericytes, highlighting the interaction between these molecules.

Interestingly, the researchers found that donors with higher blood SMAD3 levels had less vascular damage and better outcomes related to Alzheimer's disease. However, more research is needed to determine the impact of SMAD3 levels in the brain on SMAD3 levels in the blood.

Moving forward, the researchers intend to explore the role of the SMAD3 molecule in vascular and neurodegenerative outcomes associated with Alzheimer's disease. They also aim to investigate other molecules that may contribute to maintaining the blood-brain barrier.

This groundbreaking research, published in Nature Communications, provides valuable insights into the molecular mechanisms behind blood-brain barrier dysfunction in Alzheimer's disease. The identification of these unique molecular changes paves the way for the development of novel biomarkers for early diagnosis and potential therapeutic interventions.

This study was funded in part by a federal grant focused on Alzheimer's disease treatment. The research received support from the National Institutes of Health, the National Institute on Aging, the Alzheimer's Association Zenith Fellows Award, and the Mayo Clinic Center for Regenerative Biotherapeutics. The findings offer hope for the millions of individuals living with, or at risk of developing, Alzheimer's disease.