Alzheimer's Plaques Interacts with Blood Clotting Agent, Reducing Brain Blood Flow
One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid plaques between nerve cells in the brain. These are made of protein fragments snipped from an amyloid precursor protein which, in a healthy brain, are broken down and eliminated. In Alzheimer’s disease, these fragments accumulate to form hard, insoluble plaques. Scientists believe that the main element of these plaques interact with a blood clotting agent to form irregular clots, which can reduce blood flow to the brain, starving them of oxygen and contributing to deterioration of memory.
Abnormal Fibrinogen Clots Harder To Break Down
“There has been a suggestion that vascular dementia and Alzheimer’s disease might be related,” says researcher Sidney Strickland, head of the Laboratory of Neurobiology and Genetics at The Rockefeller University. “Our current work provides a possible connection between the two.”
New experiments from Rockefeller are focusing on how amyloid-beta proteins affect the blood vessels feeding the brain and how this further affects the pathology of Alzheimer’s, as simply the presence of amyloid plaques do not explain the entire disease process. The work expands on earlier research from the same research lab.
Lead researcher Hyung Jin Ahn, a postdoctoral associate, and colleagues used biochemical tests to focus on a particular form of amyloid-beta called AB42 which interacts with the blood clotting agent fibrinogen. Their findings show that the interaction between the two substances may induce abnormal fibrin clot formations which are more difficult to break down than typical blood clots.
The decreased blood flow from these clots cause cognitive dysfunction and inflammation of the neurons (brain cells).
This is a promising therapeutic angle, says Strickland. “And what’s nice is that a drug that disrupted this particular interaction would not affect clotting elsewhere like regular anticoagulants, because the amyloid-beta peptide is primarily found in the brain.”
Ahn and colleagues are now furthering their research to identify small molecules that can inhibit the Aβ42-fibrinogen interaction and hopefully these inhibitors could become an effective drug therapy for patients with Alzheimer's disease to cure the disease or at least slow progression.
H. J. Ahn, D. Zamolodchikov, M. Cortes-Canteli, E. H. Norris, J. F. Glickman, S. Strickland. Alzheimer's disease peptide -amyloid interacts with fibrinogen and induces its oligomerization. Proceedings of the National Academy of Sciences, 2010; 107 (50): 21812 DOI:10.1073/pnas.1010373107
Marta Cortes-Canteli, Justin Paul, Erin H. Norris, Robert Bronstein, Hyung Jin Ahn, Daria Zamolodchikov, Shivaprasad Bhuvanendran, Katherine M. Fenz and Sidney Strickland. Fibrinogen and β-Amyloid Association Alters Thrombosis and Fibrinolysis: A Possible Contributing Factor to Alzheimer's Disease. Neuron, Volume 66, Issue 5, 695-709 (June 10, 2010) DOI:10.1016/j.neuron.2010.05.014