Axel Montagne, PhD, on Solving Alzheimer’s and Dementia with Blood-Brain Barrier Repair

The podcast episode titled Axel Montagne, PhD, on Solving Alzheimer’s and Dementia with Blood-Brain Barrier Repair presents a new paradigm suggesting that Alzheimer's and dementia are vascular diseases caused by the breakdown of small blood vessels in the brain that supply oxygen and nutrients to neurons. Researchers use Magnetic Resonance Imaging to measure the "leakiness" of the brain vessels, and the MRI technique can predict future cognitive decline in Alzheimer's patients. Loss of pericytes, which wrap around blood vessels, leads to flow problems and cognitive decline, and targeting endothelial cells or pericytes directly through gene and stem cell therapy could prevent cognitive decline. There is a need to target inflammation in the vasculature to maintain the integrity of the barrier, and lifestyle factors such as omega-3 have been shown to regulate blood-brain barrier function. The podcast episode highlights the importance of exercise in maintaining healthy brain function and preventing small vessel disease, as small vessel disease can cause cognitive impairments. There are ongoing studies to determine the relationship between small vessel disease, blood-brain barrier breakdown, and Alzheimer's disease, and to develop treatments to prevent or slow the progression of these conditions.

The episode also discusses the significance of fibrinogen, an inflammatory marker that shouldn't be in the brain, and how extravascular deposition of fibrinogen indicates a breakdown of the blood-brain barrier that causes damage to neurons and oligodendrocytes. Fibrinogen activates brain resident immune cells that can induce over-inflammation, which is detrimental to brain functions. Studies have shown that omega-3 can blunt the white matter dysfunction caused by fibrinogen in animal models. Air pollution is a significant risk factor for dementia and can cause blood-brain barrier breakdown and microglia activation leading to inflammation. Additionally, the episode covers drugs' impact on cognition and the importance of early intervention for Alzheimer's disease.

The episode highlights the role of vascular function in cognitive health and neurodegenerative diseases such as dementia and Alzheimer's. Researchers are developing biomarkers to detect early signs of cognitive decline, and the podcast emphasizes the importance of identifying early biomarkers for early detection, prevention, and treatment of cognitive decline. The ultimate goal is to develop a better understanding of these issues and target drug interventions for people with dementia and Alzheimer's disease.