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**The Hindu: Barrier Breakdown? New Research Points to Blood Vessels as Potential Starting Point for Alzheimer’s, Other Brain Diseases**
**May 25, 2025 (IST)** – New research is challenging the traditional view that neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS originate solely with neuron damage. Two studies, published in *Science Advances* and *Nature Neuroscience*, suggest the breakdown of the blood-brain barrier (BBB), a protective layer of cells lining blood vessels in the brain, could be an initial trigger.
The BBB’s role is to shield the brain from toxins and pathogens. Researchers found that damage to the endothelial cells forming the BBB, even caused by a single point mutation in the TDP-43 protein, can lead to leakage, brain inflammation, and cognitive decline in mice. Further analysis of human brain tissue revealed similar patterns of reduced TDP-43 in endothelial cells of patients with neurodegenerative conditions.
“Endothelial cells are the first cells exposed to what we eat, what infections we carry, or even the medications we take,” said Ashok Cheemala, lead author of the *Science Advances* study. His team’s work highlights how damage to these cells can trigger inflammation and eventual neuron death.
The findings open up possibilities for earlier diagnosis and potentially preventative interventions. Researchers are exploring blood-based biomarkers, such as the HDGLF2 protein and exosomes, which could indicate BBB damage long before noticeable symptoms appear. Identifying individuals at risk in these early stages could dramatically improve the chances of slowing or even halting the progression of these devastating diseases.
Jemeen Sreedharan from King’s College London noted, “It’s compelling to think a disease we’ve long considered neuron-specific may actually start in the vasculature.” Further research is needed to determine if BBB damage is specific to neurodegenerative diseases or a more general response to brain injury.
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