Existing blood thinner delays Alzheimer’s disease in mice

Aging
An existing blood thinner — used to prevent the formation of blood clots in people at risk of stroke — could help delay the development of Alzheimer’s disease, according to a new study in a mouse model.
older woman lifting a pill container
Could a common blood thinner help people with Alzheimer’s disease?

Alzheimer’s disease is the most common form of dementia, a neurodegenerative condition in which people experience progressive memory loss.

Some treatments can help people with Alzheimer’s disease manage this symptom and others to a certain extent.

However, there is currently neither a cure nor a tried and true method of preventing the condition.

This is why researchers worldwide continue to search for strategies and therapies that could at least delay the onset of Alzheimer’s symptoms.

This is also what a team of investigators — many from the Centro Nacional de Investigaciones Cardiovasculares (CNIC), in Madrid, Spain, and The Rockefeller University, in New York — has recently investigated.

In a new study, coordinated by Marta Cortés Canteli, Ph.D., the team has used a known anticoagulant, a drug that prevents blood clots, to slow the onset of Alzheimer’s disease symptoms in a mouse model.

The researchers took this approach because previous studies have shown that individuals with this condition also tend to have poor circulation in the brain.

In the new study paper — which appears in the Journal of the American College of Cardiology — Cortés Canteli and colleagues explain that just 1 year’s treatment with this drug resulted in no memory loss and no reduction in cerebral blood flow in a mouse model of the disease.

“This discovery marks an important advance toward the translation of our results to clinical practice to achieve an effective treatment for Alzheimer disease,” says Cortés Canteli.

Significant reduction in Alzheimer’s markers

In the current study, the researchers worked with female mice that they had bioengineered to become prone to developing Alzheimer’s-like symptoms later in life.

To these mice and a control group, the investigators administered either a placebo or dabigatran etexilate, a blood thinning drug, mixed with regular chow over a period of 1 year.

The researchers calculated that each mouse in the treatment group received an average dose of around 60 milligrams of dabigatran per kilogram of body weight over 24 hours.

Mice that received this treatment for 1 year developed no memory loss and maintained normal cerebral blood flow.

Moreover, the researchers found a significant reduction in typical biological markers of Alzheimer’s disease in the mice that had received the drug.

Specifically, these mice had a 23.7% reduction in the extent of amyloid plaques, which are buildups of toxic protein. The researchers also found a 31.3% reduction in aggressive immune brain cells called phagocytic microglia and a 32.2% reduction in infiltrated T cells, another type of immune cell.

These reductions indicate lower rates of inflammation and blood vessel injury in the brain, as well as less protein buildup that disrupts normal communication between brain cells.

“Winning the battle against Alzheimer disease will require individualized combination therapy targeting the various processes that contribute to this disease,” notes Cortés Canteli.

“One goal is to improve the cerebral circulation, and our study shows that treatment with oral anticoagulants has the potential to be an effective approach in Alzheimer patients with a tendency to coagulation,” she adds.

Dabigatran is all the more promising as a potential new treatment for Alzheimer’s because it has already been approved as a treatment for other conditions and health events, and it reportedly has fewer side effects than other anticoagulant drugs.

Future studies, the researchers suggest, should develop better ways of finding out which people with Alzheimer’s disease are also prone to developing blood clots. This cohort, they explain, may benefit most from a treatment that includes anticoagulants such as dabigatran.

An individualized treatment strategy such as this will first require the development of a diagnostic tool to identify those Alzheimer patients with a tendency to coagulation. This will be an important line of research in the coming years.”

Marta Cortés Canteli, Ph.D.

“Neurodegenerative diseases are very closely linked to disease in the cerebral blood vessels,” lead author and general director of CNIC Dr. Valentín Fuster notes.

“The study of the links between the brain and heart is the major challenge for the next 10 years,” he predicts.

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