doi:10.1038/nindia.2014.25 Published online 19 February 2014
The peptide amyloid-beta, whose deposits in the brain are known to trigger Alzheimer's disease, strongly stimulate blood platelets and lead to clotting, according to new research1 . The study found a small protein RhoA as the mediator in the process. RhoA could thus act as a novel drug target in the treatment of Alzheimer's disease and unravel the possible cause of clotting abnormalities seen in these patients.
In the elderly, Alzheimer's disease is the most common cause of decline of mental processes and loss of memory. Although deposit of a small peptide called 'amyloid-beta' in the brain is known to be responsible for the disease, the underlying molecular mechanism has been largely unknown.
Platelets — blood cells that stop bleeding at an injury site — are the major source of a protein that helps make amyloid-beta in blood. Researchers at Banaras Hindu University identified target molecules of amyloid-beta in cells using platelets as peripheral model of neurons. Their study showed that amyloid-beta was able to strongly stimulate platelets leading to aggregate formation. Intravenous administration of the peptide in mouse accelerated thrombus formation in pulmonary vessels.
The effect of amyloid-beta on platelets was found to be mediated through activation of RhoA,a small GTP-binding protein responsible for cytoskeletal reorganization in cells, and that inhibition of RhoA by a specific pharmacological agent reversed the effects of amyloid-beta on platelets.
Patients of Alzheimer's also have clotting abnormalities, which could be explained by amyloid-beta-induced activation of platelets, says lead researcher Debabrata Dash.