Does blood vessel damage cause neurodegeneration?

• Neurodegenerative diseases like Alzheimer’s and Parkinson’s damage neurons, leading to memory loss, confusion, and loss of independence.

• Two recent studies suggest that damage to the blood-brain barrier (BBB) may be the first domino to fall in neurodegenerative diseases.

• The BBB, made up of tightly packed endothelial cells, line blood vessels in the brain and are the first cells exposed to harmful substances.

• If these cells become inflamed or damaged, the barrier becomes leaky, allowing harmful substances to slip into the brain and trigger inflammation.

• This inflammation can lead to neuron death, causing memory loss and cognitive decline.

• The TDP-43 protein, which regulates RNA and ensures proper gene expression inside cells, goes rogue in people with neurodegenerative diseases.

• Researchers used genetically modified mice carrying a disease-causing mutation in the Tardbp gene that encodes TDP-43 to investigate.

• Key proteins holding the BBB together, like claudin-5 and VE-cadherin, were lost, allowing molecules from the bloodstream to leak into brain tissue.

• The team also analyzed over 1,30,000 individual brain-cell nuclei from postmortem human brain samples from 92 donors aged 20-98.

• The findings suggest that a disease we’ve long considered neuron-specific may actually start in the vasculature.