Image by Andre E.X. Brown
Antiplatelet drugs can significantly reduce amyloid plaques in cerebral vessels of transgenic mice with Alzheimer’s disease, according to new research.
The study revealed a mechanism for direct involvement of platelets in the progression of Alzheimer’s disease, and investigators believe this could be of great importance for the treatment of Alzheimer’s patients.
Alzheimer’s disease is characterized by the formation of amyloid aggregates and deposits of amyloid in the brain. The amyloid deposits damage the structure and function of nerve tissue in the brain and lead to the loss of neuronal cells and cognitive capability.
Amyloid deposits in Alzheimer’s disease occur not only in the brain parenchyma, but also in blood vessels in the brain. The current study, published in Science Signaling, deals with the vascular form of the disease.
Previous research demonstrated that platelets attach to amyloid deposits in the vessel wall, which leads to ongoing platelet activation in mice. The platelets then form a hemostatic plug, which occludes vessels in the brain and leads to insufficient perfusion of the surrounding tissue.
Investigators have now determined that the protein amyloid-ß binds to a specific integrin on the platelet surface that is important for the aggregation of platelets.
This binding induces the release of adenosine diphosphate and the chaperone protein clusterin and supports the formation of amyloid plaques.
In cell culture experiments, the investigators analyzed platelets from 5 patients with Glanzmann’s thrombasthenia, a hereditary defect of platelet activation, and found no amyloid plaques.
The team then treated Alzheimer’s transgenic mice with the antiplatelet agent clopidogrel. The mice exhibited reduced platelet activation and significantly reduced amyloid plaque formation, which improved the perfusion of the brain during the 3-month treatment with the drug.
The investigators suggest that antiplatelet therapy may alleviate fibril formation in cerebral vessels of Alzheimer’s disease patients.
