New protein may play a role in Alzheimer's disease
A new study suggests that a previously unknown protein may play a fundamental role in the pathogenesis of Alzheimer's disease. The research, led by scientists at Case Western Reserve University, says the new protein facilitates the formation of amyloid plaques, which are thought to be the main cause of the neurodegeneration associated with the disease.
A protein that was previously unknown
Despite a number of failures in clinical trials, the dominant causal hypothesis for Alzheimer's disease is that the accumulation of toxic plaque amyloid protein deposits is the primary pathological source of the disease. However, it remains unclear how and why these amyloid deposits form.
This new research describes the systematic process of first discovering a potentially new protein and then experimentally studying its action in animal studies.
"We are very excited about this because our study is probably the first systematic work combining the identification of high-dimensional brain imaging data from a genome-wide association study with experimental validation in Alzheimer's disease," says Xiaofeng Zhu, a researcher working on the project.
After identifying a specific gene related to Alzheimer's disease brain atrophy, the researchers focused on a particular protein encoded by this gene. The researchers found that this protein binds directly to amyloid peptides and facilitates the formation of toxic plaques.
This protein accumulates at the centre of the plaque in Alzheimer's disease patients, which is part of the reason why we called it "aggatin,"" says Xinglong Wang, another researcher working on the project.
The protein called aggatin is believed to be essential for the formation of amyloid plaques.
Several subsequent experiments on mice revealed that the aggregate protein was essential for the formation of amyloid plaques in the brain of an animal. When aggregate was injected into the animal brains, the formation of plaques accelerated, as did cognitive dysfunction. Whereas when the aggregate was removed, the opposite occurred: plaque formation decreased and cognitive dysfunction disappeared.
This work still has a long way to go before translating into clinical treatment in humans. The gene that codes for aggregatin, called FAM222A, has been linked to atrophied regions of the brain in human patients with Alzheimer's disease. But the activity of this protein in human subjects with Alzheimer's disease is still unclear.
The next step will be to test these mechanisms in both animal models and human subjects. Researchers then hope that therapeutic results can be developed, leading to clinical trials in humans.
A new risk factor
"Based on the data we have, this protein may be a new and unrecognized risk factor for Alzheimer's disease," says Wang. "We also see it as a potential new therapeutic target for this devastating disease.
