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Tissue Model Reveals Role Of Blood-Brain Barrier In Alzheimer’s

Hematology
Blood-brain barrier
Hematology- Oncology

The researches find that the Beta-amyloid plaques, the protein aggregates that form in the brains of Alzheimer’s patients, disrupt many brain functions and can kill neurons. Therefore They can also damage the blood-brain barrier the normally tight border that prevents harmful molecules in the bloodstream from entering the brain. MIT engineers have now developed a tissue model that mimics beta-amyloid’s effects on the blood-brain barrier; and used it to show that this damage can lead molecules such as thrombin, a clotting factor normally found in the bloodstream; to enter the brain and cause additional damage to Alzheimer’s neurons.

Damage the blood-brain barrier

“They are able to show clearly in this model that the amyloid-beta secrete by Alzheimer’s disease cells actually impair barrier function, and once that is impair; factors are secrete into the brain tissue that can have adverse effects on neuron health,” says Roger Kamm; the Cecil and Ida Green Distinguished Professor of Mechanical and Biological Engineering at MIT. The researchers also use the tissue model to show that a drug that restores the blood-brain barrier can slow down the cell death seen in Alzheimer’s neurons.

Kamm and Rudolph Tanzi; a professor of neurology at Harvard Medical School and Massachusetts General Hospital; are the senior authors of the study, which appears in the journal Advanced Science. MIT postdoc Yoojin Shin is the paper’s lead author. The blood vessel cells that make up the blood-brain barrier have many specialized proteins that help them to form tight junctions cellular structures that act as a strong seal between cells.

Junctions cellular structures

Alzheimer’s patients often experience damage to brain blood vessels caused by beta-amyloid proteins; an effect known as cerebral amyloid angiopathy (CAA). It is believed that this damage allows harmful molecules to get into the brain more easily. Kamm decided to study this phenomenon, and its role in Alzheimer’s; by modeling brain and blood vessel tissue on a microfluidic chip.  “What we were trying to do from the start was generate a model that; we could use to understand the interactions between Alzheimer’s disease neurons and the brain vasculature;” Kamm says.

“Given the fact that there’s been so little success in developing therapeutics that are effective against Alzheimer’s; there has been increased attention paid to CAA over the last couple of years.” His lab began working on this project several years ago; along with researchers at MGH who had engineered neurons to produce large amounts of beta-amyloid proteins; just like the brain cells of Alzheimer’s patients.