Alzheimer's Disease Research
Marta Cortes-Canteli, Ph.D.
New York , NY, United States
Title: Role of Fibrinogen in AD Neuronal and Synaptic Loss
Non-Technical Title: Blood Circulation and Neuronal Health in the Alzheimer's Brain
Acknowledgements: This project is supported by a generous bequest from the Richardson‐ Sargent Family Trust and the Richardson‐Sargent Credit Shelter Trust.
Duration: July 1, 2011 - June 30, 2013
Award Type: Pilot
Award Amount: $150,000
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.
Cortes-Canteli*, M., Paul*, J., Norris, E.H., Bronstein, R., Ahn, H.J., Zamolodchikov, D., Bhuvanendran, S., Fenz K.M. and Strickland. S. (2010) Fibrinogen and beta-amyloid association alters thrombosis and fibrinolysis: a possible contributing factor to Alzheimer's disease. Neuron 66, 695-709. *Contributed equally. Selected for issue's cover.
Ahn, H.J., Zamolodchikov, D., Cortes-Canteli, M., Norris, E.H., Glickman J.F. and Strickland. S. (2010) Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci U S A. 107, 21812-7.
Cortes-Canteli M, Zamolodchikov D, Ahn HJ, Strickland S, Norris EH. Fibrinogen and altered hemostasis in Alzheimer's disease. J Alzheimers Dis. 2012 Jan 1;32(3):599-608. doi: 10.3233/JAD-2012-120820.
Alzheimer’s disease is a complex neurodegenerative disorder that affects millions of people and for which there is no effective treatment. A large body of research implicates vascular pathology (problems with blood vessels) as a contributing factor in this disease, as patients have disrupted blood circulation in their brains. Dr. Cortes-Canteli’s team has been investigating the role of fibrinogen, the major component of blood clots, in Alzheimer’s disease. So far, the team has detected this protein in the same areas where the neurons are dying. To analyze if the presence of fibrinogen is affecting neuronal viability, they altered its levels in mice with Alzheimer’s disease and checked if the neurons become healthier or sicker. In the future, the lab will design and test a drug to interfere with fibrinogen’s interaction with beta-amyloid, a molecule involved in Alzheimer’s disease pathogenesis.
Dr. Marta Cortes-Canteli is a research associate in the Laboratory of Neurobiology and Genetics at The Rockefeller University. She obtained her Ph.D. in biochemistry at the University of Madrid and performed postdoctoral work there for three years. She then obtained a postdoctoral position at The Rockefeller University where she was named a Women & Science Fellow. She later was awarded an Alzheimer's Disease Research Fellowship from BrightFocus. Her studies focus on one of the least known aspects of Alzheimer's disease: how blood circulation and blood clot formation affect the disorder.