Blood-clotting factor may cause Alzheimer's disease

A protein known for its role in forming blood clots has been found to cause the characteristic cognitive decline of Alzheimer's disease. The discovery provides a new target for drug developers trying to find a cure for this devastating condition.

Blood vessels in brainUGREEN 3S | Shutterstock

Alzheimer's disease is the most common cause of dementia, with over half a million sufferers in the UK alone. It is a progressive disease characterized by memory loss and difficulties with thinking, problem-solving or language.

The condition is characterized by a reduction in the number of connections between neurons in the brain, caused by  the build-up of proteins as ‘plaques’ and ‘tangles’. Eventually, the build-up of these proteins results in of the breakdown of synapses and cognitive decline.

Studies have previously shown abnormalities in the vast network of blood vessels in the brain, but was not clear whether the vascular damage contributed to synaptic damage or whether it caused neuroinflammation, both of which can lead to cognitive decline.

Now, using state-of-the-art imaging technology, scientists at the Gladstone Institutes have produced the first three-dimensional volume images of Alzheimer’s disease. The images are of the brains of patients with Alzheimer's disease and also mouse models.

The findings showed that the blood-clotting protein, fibrinogen, is responsible for a series of molecular and cellular events that can destroy memory storage sites in the brain, giving rise to cognitive decline. Fibrinogen was seen to leak from the blood into the brain, where it activated the brain's immune cells triggering them to destroy neuronal synapses.

The researchers demonstrated in mouse models of Alzheimer’s disease that preventing fibrinogen from activating the brain’s immune cells provided protection against memory loss.

We found that blood leaks in the brain can cause elimination of neuronal connections that are important for memory functions. This could change the way we think about the cause and possible cure of cognitive decline in Alzheimer's disease and other neurological diseases."

Katerina Akassoglou, Lead Investigator

The team also showed that fibrinogen was able to cause the same effect in healthy brains, without any signs of amyloid plaques, which have been the main focus in the search for effective treatments for Alzheimer's disease.

Our work identifies an alternative culprit that could be responsible for the destruction of synapses."

Mario Merlini, First Author

Indeed, the data confirm that there are two distinct mechanisms underlying dementia. This helps explain why elderly people with vascular dementia show similar rates of cognitive decline as patients with the amyloid plaques of Alzheimer's disease and why an additive effect is observed in patients with both pathologies.

It is hoped that these exciting findings, which have greatly advanced our understanding of the contribution of vascular pathology to the progression of Alzheimer's disease, may have therapeutic implications not only in Alzheimer's disease but also in other neurological conditions with similar pathologies such as multiple sclerosis.

Akassoglou and her colleagues have already developed an antibody that blocks the interaction between fibrinogen and cells of the brain's immune system and protected mouse models of Alzheimer's disease from brain inflammation and neuronal damage.

Kate Bass

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Kate Bass

Kate graduated from the University of Newcastle upon Tyne with a biochemistry B.Sc. degree. She also has a natural flair for writing and enthusiasm for scientific communication, which made medical writing an obvious career choice. In her spare time, Kate enjoys walking in the hills with friends and travelling to learn more about different cultures around the world.

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Comments

  1. Steven Kelley Steven Kelley United States says:

    I just read your article and it made sense to me. Which is why i can't understand why you have not gotten the handle on this yet. Have you ever tried the wash dishes with the washing machine running? When the washing machine is filling up the water pressure in the kitchen sick is barely there. Basically the water just fall out of the faucet into the sink. No force behind the water coming out of the faucet. Because of the lack of pressure not all of the crap cleaned off the dishes is washed out of the sink trap. Leaving a little remnants of the substance left from washing dish behind. Each time the dish are washed without the water pressure the remnants builds up over time.

    What i am saying is the blood clots are the washing machine cutting off proper blood flow pressure.Thereby causing the TAU tangles and Beta-Amyloid to not be completely flushed from the system. Leaving remnants that over time builds up to began causing physical problems. All these drugs being tested will not truly work, because they are trying to cure the effect and not the cause. Until the blood clots are taken care of and proper blow flood restored. Then they will not succeed with any cure that does not consist of a cure for the white blood cell clotting first. The return of proper blood flow will help with more than one of the drugs that fail to meet the TAU tangles and Beta-Amyloid levels needed to pass the FDA.

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