Researchers have untangled some of the neurological events that may ultimately lead to Alzheimer's disease. Two new studies show that a protein implicated in this form of dementia can infect other neurons to spread disease across the brain. These problematic proteins clump together, which can lead to cognitive problems.
A protein's shape—the way its chains of amino acids fold—determines its function. If a protein misfolds, its structure and function change. In Alzheimer's, researchers have long suspected that misfolded versions of a protein called amyloid-beta might travel from cell to cell and cause more amyloid-beta proteins to take on a deformed shape.
To test this idea, biophysicist Jan Stöhr of the University of California, San Francisco, and his colleagues injected synthetic amyloid-beta proteins into the brains of mice and found that plaques began to form in less than six months. Even when the synthetic proteins were injected into only one side of the brain, over time plaques materialized throughout the organ, the researchers found. “If these aggregates are not cleared by the brain, they will start to recruit more amyloid-beta peptides into the diseased conformation, and the spread throughout the brain begins,” Stöhr says. The results appeared in the June Proceedings of the National Academy of Sciences USA.
In a separate study using a cell culture, a team of researchers led by Martin Hallbeck of Linköping University in Sweden tracked amyloid-beta transmission from neuron to neuron for the first time. The results, published in the June 27 Journal of Neuroscience, also show that neurons containing misfolded amyloid-beta can cause neighboring, connected neurons to break down, eventually infecting the entire culture.
The current task for scientists is to figure out what other proteins and cellular machinery assist the infection process. Targeting these helpers may be an effective option for developing Alzheimer's therapies, Stöhr says.
Labels: amyloid-beta-proteins, jan-stohr, proceedings-of-the-national-academy-of-science, ucsf