New discoveries on beta-amyloid may lead to a better treatement for Alzheimer’s

Researchers at Stanford University School of Medicine in collaboration with Harvard University have made new discoveries about Alzheimer’s disease ( AD) that could lead to the development of new therapies. It seems that beta- amyloid, a well known protein that is involved in Alzheimer’s, begins to destroy synapses before they aggregate in plaques ( one of the hallmarks of AD).

Statistics show that there are 5 million people suffering from Alzheimer’s disease and it is estimated that these numbers will increase in the future. There are two important features in Alzheimer’s disease : synapse loss and impaired cognitive functions such as memory. Carla Shatz , PhD, professor of neurobiology and of biology and senior author of the study , noted that their findings suggest that Alzheimer’s disease begins to manifest long before the formation of beta -amyloid plaques.

Experiments on laboratory animals and human brain tissue explain why clinical trials in recent years  failed in their attempt to stop the progression of Alzheimer’s disease by targeting these beta -amyloid plaques. The research also could provide the basis for new more effective therapies. Beta amyloid, although initially isolated , has a tendency to form aggregates or plaques, which alter nerve cells.

  The study led by researchers at Stanford University and Harvard University is the first to show that the clustered form of beta amyloid destroys synapses by binding to a receptor on neurons. Synapses, which are communications between neurons, are extremely important in the normal functioning of the brain; they have a role in memory storage, processing emotions and thoughts, etc. Researchers observed during laboratory experiments  that, if mice lack a protein located very close to the synapses, they were resistant to breakdown memory and synapse loss. The study showed for the first time that this protein, called PirB, is a receptor for the clustered form of beta -amyloid. In other words,  PirB binds very tightly to beta amyloid leading to a whole series of events that ultimately results in the destruction of synapses.

Also, in another experiment conducted by Taeho Kim , PhD, a postdoctoral scholar in Shatz ‘s lab and the lead author of the new study, researchers compared the proteins in the brains PirB – expressing Alzheimer ‘s mice with the PirB – lacking Alzheimer ‘s mice. They noted that in the latter, a certain enzyme called cofilin have an increased activity. This observation has also been highlighted by other studies that showed that cofilin activity is significantly higher in patients with Alzheimer’s disease compared to patients without Alzheimer’s disease. Now, based on these new discoveries, researchers hope to develop better therapies for treating Alzheimer.