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More on Fibrinogen and Blood-Brain Barrier Leakage in the Aging Brain


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Posted 13 February 2019 - 11:12 AM


The blood-brain barrier lines the blood vessels of the brain, and only very selectively allows passage of molecules to and from the brain. As is the case for all tissue structures, it fails with age. Molecular damage and cell dysfunction causes it to become leaky, and as a consequence all sorts of cells and proteins make their way into the brain to cause damage. One of these is fibrinogen, which appears toxic to brain cells. Here, researchers elaborate on previous findings, suggesting that this is an immune activation problem, and may be a significant cause of neurodegenerative conditions that exhibit significant loss of synapses, such as Alzheimer's disease.

Researchers used state-of-the-art imaging technology to study both mouse brains and human brains from patients with Alzheimer's disease. They also produced the first three-dimensional volume imaging showing that blood-brain barrier leaks occur in Alzheimer's disease. They found that fibrinogen, after leaking from the blood into the brain, activates the brain's immune cells and triggers them to destroy important connections between neurons. These connections, called synapses, are critical for neurons to communicate with one another.

Previous studies have shown that elimination of synapses causes memory loss, a common feature in Alzheimer's disease and other dementias. Indeed, the scientists showed that preventing fibrinogen from activating the brain's immune cells protected mouse models of Alzheimer's disease from memory loss. "We found that blood leaks in the brain can cause elimination of neuronal connections that are important for memory functions. This could change the way we think about the cause and possible cure of cognitive decline in Alzheimer's disease and other neurological diseases."

The team showed that fibrinogen can have this effect even in brains that lack amyloid plaques, which are the focus of diverse treatment strategies that have failed in large clinical trials. The researchers showed that injecting even extremely small quantities of fibrinogen into a healthy brain caused the same kind of immune cell activation and loss of synapses they saw in Alzheimer's disease. Interestingly, researchers recently developed an antibody that blocks the interaction between fibrinogen and a molecule on the brain's immune cells. In a previous study, they showed this antibody protected mouse models of Alzheimer's disease from brain inflammation and neuronal damage.

Link: https://gladstone.or...heimers-disease


View the full article at FightAging




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