Impact of Tau Protein on Brain Vascular Health in Alzheimer's Disease

Recent research from Temple University's Lewis Katz School of Medicine has uncovered a critical mechanism by which tau protein contributes to vascular impairment in Alzheimer's disease. The study reveals that a harmful form of tau, known as protofibrillar tau, can directly damage the blood vessels in the brain. This damage occurs through alterations in how the endothelial cells—the cells lining blood vessels—produce energy, leading to increased inflammation and a weakened blood-brain barrier, which is vital for protecting the brain.

Examining this process, researchers exposed in vitro models of brain vasculature to protofibrillar tau and observed that it compromised the integrity of the blood-brain barrier, making it more 'leaky' and less effective at safeguarding neural tissue. The cells responded swiftly, changing their energy metabolism, which triggered inflammatory responses and further deteriorated barrier function. These early changes in endothelial cell metabolism suggest that vascular damage happens early in the progression of Alzheimer's disease.

The team also confirmed their findings in mouse models engineered to accumulate tau, demonstrating that tau's effect on blood vessel cells can occur before significant neural degeneration. Their work highlights key molecular and metabolic changes induced by tau that lead to increased permeability and inflammation of the vascular lining. Understanding these early vascular alterations opens new avenues for therapeutic intervention aimed at preserving blood-brain barrier integrity and potentially slowing Alzheimer’s progression.

Future research aims to investigate how tau enters endothelial cells and influences their energy pathways, as well as its effects on glial support cells in the neurovascular unit. Such insights are essential for developing strategies to combat tau-related neurovascular damage and improve outcomes for patients with Alzheimer's disease.

Source: https://medicalxpress.com/news/2025-04-tau-protein-weakens-brain-vascular.html