09 Oct Long Term Treatment With Dabigatran Reduces Alzheimer’s Symptoms in Mouse Model
MedicalResearch.com Interview with:
Marta Cortes Canteli, PhD
Miguel Servet Research Fellow
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
MedicalResearch.com: What is the background for this study?
Response: Alzheimer´s disease is the most common form of dementia affecting more than 30 million people worldwide. Research in recent years has linked the disease to a reduction in the cerebral circulation; this results in an insufficient supply of nutrients and oxygen to brain cells, leading to their death. Alzheimer disease is also known to be linked to an underlying chronic prothrombotic state. The present study combined physiological and molecular analyses to demonstrate that long-term anticoagulation effectively slows disease progression in a transgenic mouse model of Alzheimer disease.
MedicalResearch.com: What are the main findings?
Response: The main findings are that long-term anticoagulation with dabigatran, an already approved direct oral anticoagulant, inhibits the abnormal formation of fibrin clots in the Alzheimer´s disease brain, hence preserving blood flow and facilitating oxygen and nutrient delivery to the brain. This drug, in turn, also has a beneficial effect on controlling neuroinflammation, maintaining the integrity and functionality of the blood brain barrier and reducing amyloid, the main pathological hallmark of Alzheimer´s disease.
MedicalResearch.com: What should readers take away from your report?
Response: Long-term treatment with an oral direct anticoagulant ameliorates Alzheimer´s disease pathogenesis in a mouse model of the disease. A pro-thrombotic state is among the mechanisms contributing to Alzheimer´s disease pathogenesis and should be taken into account during diagnosis and treatment.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Alzheimer´s disease is a multifactorial disorder. If we want to win the battle against it, efforts should be focused toward the development of multidrug individualized therapies targeting the various processes contributing to an individual’s pathology instead of the “1 target, 1 treatment” approach that has not been successful thus far. Our studies indicate that one of the pathological mechanism worth targeting in Alzheimer´s disease is the pro-coagulant state that, in combination with other disease-modifying compounds, might be instrumental in improving Alzheimer´s disease pathogenesis.
MedicalResearch.com: Is there anything else you would like to add?
Response: Our findings need to be replicated in other animal models, especially in large animals, to ensure robustness and support clinical trials of antithrombotic therapy for prevention or amelioration of Alzheimer´s disease. It is also important to mention that the use of anticoagulants has the important limitation of the increased incidence of bleeding associated with its use. This is especially critical in the frail and elderly Alzheimer´s disease patients who are prone to develop intracerebral hemorrhages. Dabigatran is one of the oral direct anticoagulants that presents a low risk of intracranial bleeding, but the risk is still present and dosing will need to be carefully evaluated by a heart–brain team of experts to ensure its use outweighs any bleeding risk.
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