Role of Fibrinogen in AD Neuronal and Synaptic Loss
The association between fibrinogen and Abeta affects normal hemostasis. Determining if fibrinogen also influences the neuronal and synaptic loss present in Alzheimer's disease is substantially important as it will support the design of therapeutic strategies aimed at blocking that association.
People who have Alzheimer's disease can also have blocked brain blood vessels that accelerate problems with memory and other brain activities. In a previous BrightFocus grant, Dr. Cortes‐Canteli and collaborators showed that beta‐amyloid protein binds to the blood clotting protein, called fibrinogen, and prevents it from busting‐up clots. The resulting block in blood flow can lead to increased inflammation, loss of communication between nerves, and death in those parts of the brain. Moreover, decreasing the amount of fibrinogen has been shown to reduce memory loss in mouse models of Alzheimer's disease. In this project, Dr. Cortes‐Canteli will study mouse and human brain samples to determine whether fibrinogen is found in the same locations where nerve cells stop communicating. They will also treat Alzheimer's disease mice with drugs that decrease fibrinogen levels to check whether the neurons communicate better once clots are removed and blood flow has been restored. It is extremely important to prevent neurons from dying, and this work will give clues on how to prevent it and will support the design of therapeutic strategies aimed at blocking or decreasing the blood clot formation observed in Alzheimer's disease.