Low Level of Key Proteins May Play Role in Alzheimers Memory
In the most recent CDC statistics released this month, the rate of Alzheimer’s disease has significantly increased since 2003. The Alzheimer’s Association notes that the disease stands out among the others because there is currently no effective treatment or a way to slow progression of symptoms. Researchers world-wide are trying to find the answers, and two new studies may give clues to key protein levels that appear to play a big role in memory development and loss.
Research May Lead to Alzheimer's Disease Treatments
Researchers from the Gladstone Institute of Neurological Disease in San Francisco began their study on NMDA receptors based on past research that indicates that Alzheimer’s patients may have lower levels of NMDA receptor activity, which is known to be involved in memory formation. A protein called tyrosine kinase EphB2 is known to regulate NMDA levels. The team, led by Dr. Lennart Mucke, used mice to study this further.
Some of the mice were normal and some were transgenic, meaning they had been bred to have memory and neuron-signaling problems that resemble those in humans with Alzheimer’s disease. The transgenic mice also had high levels of amyloid proteins and lower levels of EphB2. The team noted that free-floating amyloids, which are thought to contribute to memory damage and loss, bind to EphB2 and lead it to be broken down by the cell.
The scientists also depleted EphB2 from the brains of the normal mice, which led to neuron signaling problems seen in the transgenic mice. Adding EphB2 back to the transgenic mice appeared to improve neuron signaling and performance on memory and learning tests.
The results of the study, published in the journal Nature, suggest that Alzheimer's disease might someday be treated by modifying EphB2 levels or preventing its breakdown. "Based on our results, we think that blocking amyloid proteins from binding to EphB2 and enhancing EphB2 levels or function with drugs might be of benefit in Alzheimer's disease," Mucke says.
In a second study, conducted at the University of Texas Health Science Center in San Antonio, researchers found that raising levels of CREB-binding protein or CBP may improve memory in mice bred to develop Alzheimer’s. The protein also plays an essential role in cell growth and division.
Salvatore Oddo, whose study appears in the Proceedings of the National Academy of Sciences, said that boosting CBP in mice restores activity of another protein (CREB) and also increases the brain-derived neurotrophic factor (BDNF) which is needed to develop long-term memory.
Enhancing CBP would not alter amyloid beta, but it might make memory formation more efficient. "Pharmaceutical companies could theoretically work toward finding a new drug that may facilitate the expression of this CBP protein," said Oddo.
NIH author Allison Bierly PhD reminds us that although humans share many characteristics with mice, promising findings in animal models do not always translate to humans. Still, the research is a step forward in understanding Alzheimer’s disease, now the sixth leading cause of death in the United States