Researchers from the Department of Biochemistry at the Institute of Medical Sciences, Banaras Hindu University (BHU) are a step closer to preventing Alzheimer’s disease.
An effective antidote against amyloid beta peptide that causes Alzheimer’s disease and cerebral amyloid angiopathy has been found.
A team of researchers led by Prof. Debabrata Dash has demonstrated for the first time that when fibrinogen binds to amyloid beta it effectively prevents the peptide from causing any cytotoxic effects. Fibrinogen brings about this by preventing amyloid beta from interacting with cells. The results were published in the journal Molecular Medicine .
There is growing evidence that amyloid beta plays a pivotal role in synaptic loss and neuronal death resulting in cognitive decline and thus Alzheimer’s.
Like neuronal cells, platelets too carry an amyloid precurosor protein and release them as amyloid beta through the action of an enzyme. “Since platelets are easily accessible unlike neuronal cells and platelets are quite sensitive like neurons and carry many neurotransmitters, platelets are considered as a peripheral model of neurons. So we used platelets to study how fibrinogen prevented amyloid beta from stimulating the platelets,” says Prof. Dash, corresponding author of the paper.
Platelets isolated from blood and suspended in a buffer were strongly activated when amyloid beta was added. But amyloid beta was ineffective in stimulating the platelets when the researchers suspended the platelets in plasma. “So we knew that some component in the plasma was preventing the action of amyloid beta on platelets,” he says. “We finally found that fibrinogen present in the plasma was responsible for preventing amyloid beta from acting on the platelets. The toxicity of neuronal cells was also prevented in the presence of fibrinogen.”
A battery of platelet functions was studied in the presence of amyloid beta. In each case, the amyloid beta was found to stimulate the platelets to carry out the functions. “But when we added fibrinogen all the amyloid beta-induced functions of the platelets were prevented,” Prof. Dash says.
They also studied the protective effect of fibrinogen on neuronal cells. The presence of fibrinogen significantly impaired the association of amyloid beta protein with neurons. Fibrinogen even reversed the drop in neuronal cell viability in the presence of amyloid beta.
“We have identified the sequence on fibrinogen that interacts with amyloid beta,” says Dr. Paresh P. Kulkarni from the Department of Biochemistry at BHU and one of the authors of the paper.
