Marta Cortes-Canteli, Ph.D.
In the last few years, many Alzheimer’s researchers have been working under the assumption that beta amyloid, the protein that makes up Alzheimer’s plaques, damages brain cells. Other scientists, however, argue that Alzheimer’s is really due to blood vessel or vascular disease that reduces blood flow to brain cells. Maybe both are right -- people with dementia tend to have multiple pathologies in their brains, and these pathologies seem to interact to increase the risk for and severity of dementia.A new paper from researchers at The Rockefeller University suggests that a protein called fibrinogen might be involved in this interaction. Postdoctoral fellow Marta Cortes-Canteli and her colleagues focused specifically on the role of fibrinogen and beta amyloid in the presence of abnormal blood clots and the cerebral amyloid angiopathy (CAA) my father’s autopsy showed.
In CAA, deposits of beta amyloid build up on blood vessels in the brain, increasing the risk for hemorrhagic stroke and dementia. CAA and Alzheimer’s pathology often go hand in hand.
A certain amount of fibrinogen is normal (although not in the brain). When you are injured, your body needs the protein to help blood clots form to stop bleeding. But high levels of fibrinogen in the blood are linked to faster cognitive decline, at least in people diagnosed with Mild Cognitive Impairment, and to increased risk for Alzheimer’s and vascular dementia.
In a series of experiments, Dr. Cortes-Canteli and her colleagues found that:
- In the lab and in mice genetically engineered to develop Alzheimer’s pathology, the combination of beta amyloid and fibrinogen causes blood to clot more quickly, and to form clots that are more difficult for the body to break down
- In the brains of these mice, and in samples of human brains, fibrinogen can be seen in blood vessels affected by CAA
- In the same mice, reducing fibrinogen levels decreases CAA pathology and improves performance on memory tests.
In this scenario, reducing fibrinogen levels or taking blood thinning medicines to prevent clotting might treat CAA and blood flow problems. But the body needs fibrinogen, and people with CAA are already at high risk for hemorrhagic stroke, so blood thinners might be harmful. Blocking the interaction between fibrinogen and amyloid could be a better way to prevent or treat problems with memory and thinking, says Dr. Cortes-Canteli. “Targeting the “abnormal” association between amyloid and fibrinogen could be a promising therapeutic approach, since that drug would normalize any blood clots formed in the presence of amyloid, but such a drug wouldn’t have any effect on general clotting,” she wrote in an email.
Any potential treatment is a long way off. The work of Dr. Cortes-Canteli and colleagues is still theoretical, and hasn’t been tested in humans. And it’s probably too simplistic to think one medicine will treat or prevent Alzheimer’s, she warns. “Alzheimer’s is a complicated disease in which different pathological processes are occurring at the same time. Therefore, I think a combined treatment would be more effective than just treating a single pathological hallmark. The results we found indicate that one of the areas that should be therapeutically treated, in combination with others, is abnormal clot formation.”
You can learn more about this research by watching the University’s video below: