How Do Alzheimer's Disease and Vascular Dementia Interact?

Summary:   Researchers at The Rockefeller University have published a paper proposing a new model for how Alzheimer’s and vascular disease interact to worsen memory and thinking. If their theory is confirmed, medicines that block this interaction could someday be an important part of treatment for memory loss. 

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.

The researchers hypothesize that this interaction between beta amyloid and fibrinogen and the resulting abnormal blood clots reduces blood flow in the brain and increases inflammation, thereby contributing to cognitive decline.

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:

Comments

[Richard Taylor]

Hello, and thank you again for adding logic and reasoning to the grains of truth that are being discovered about how the brain works. Its as if not two grains of truth touch each other, so we use words to make the connections until we get to the claim of a treatment/pill to cure/reverse/slow down alzheimer's disease.

Unfortunately researchers (not this one) seem ready to quickly add their own words to fill in the blanks around their grain of truth discovery. And most all these grains of truth come from brains of nude mice!

Richard

[Danny George]

“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."

It feels like the field is slowly (tectonically) shifting to this stance. Multiple pathologies would indicate the need for multiple therapies, right? Unfortunately, the whole research funding world is predicated on single pathways/proteins. These structural barriers are tough to overcome