The researchers discovered that, when a molecule responsible for dialing down the immune system malfunctions in the brain cells of mice, the rodents develop symptoms of Alzheimer’s disease.
Alzheimer’s disease is characterized by an excessive buildup of proteins into plaques that are likely to cause brain cells to die and lose their connections to other neurons. However, the underlying biological problems behind Alzheimer’s are not yet understood.
Researchers in the university’s department of neurology examined slices of the brains of Alzheimer’s patients who had died, and discovered abnormally low levels of the molecule involved in the body’s response to infection. That molecule allows the brain to detect and respond to TGF-beta, a protein teeming through human bodies and involved in fighting infection.
Scientists attempted to investigate the effects of TGF-beta on neurons that could help prevent Alzheimer’s. “We tried to see what happens if we block neurons from getting this beneficial signal,” explained Tony Wyss-Coray, associate professor of neurology at Stanford University.
The mice were genetically engineered with a defect similar to the one they found in the brains of Alzheimer’s patients and had brain cells that could no longer respond to TGF-beta’s signal. Unable to receive the beneficial TGF-beta signal, the rodents showed signs of Alzheimer’s disease. Brain cells died as the mice grew older, and the cells failed to make connections to other brain cells.
In the past, researchers have tried using molecules that work like TGF-beta to provide protection against Alzheimer’s, but the proteins are too large to enter the brain through the bloodstream. To sidestep that problem, the researchers are working to identify small molecules that can boost the TGF-beta pathway in neurons.