It’s estimated that there are as many as 5.3 million Americans living with Alzheimer’s disease and is the fourth leading cause of death in the United States.
Alzheimer’s disease is characterized by neuronal cell death and a progressive loss of functioning in the brain. Symptoms of Alzheimer’s disease include memory loss, impaired judgment, language difficulties and mood or behavior changes. Beta amyloid, or Abeta is one of many proteins found to be associated with Alzheimer’s disease. It is released when a larger protein, amyloid precursor protein (APP), is cut by several enzymes, resulting in amyloid plaques, a contributing factor in Alzheimer’s disease. Research suggests this occurs when APP is abnormally processed, possibly due to trauma, cholesterol levels or oxidative stress. Thus, beta amyloid and APP are involved in the early process of Alzheimer’s disease development.
APP is also known to be present at the synapses between neurons though its molecular action is not understood. Synapse loss is thought to be one of the main contributors to the cognitive decline seen in Alzheimer’s disease.
New research now suggests that while APP is negatively associated with Alzheimer’s disease, it appears to play a critical role in brain development, and that a balance of APP is critical.
Many studies have elucidated the importance of synapses and dendritic spines, the protrusions that allow communication between brain neurons, in learning and memory. In this new research, the scientists found decreased spine density in mice that have been genetically modified to not produce APP. The scientists then looked at four-week-old mice that over produced APP and found a significant increase in spine density. At one year old, however, these mice have beta amyloid plaques, as well as a decrease in spine density due to the effect of beta amyloid, which is known to be neurotoxic.
“Our work suggests that APP balance is critical for normal neuronal development, connection of synapses, and dendritic spine development, all of which have implications for the extensive synapse loss and cognitive decline seen in Alzheimer’s disease,” explains the study’s author, Hyang-Sook Hoe. “One strategy to counteract development of Alzheimer’s disease is to maintain balance in APP protein expression in order to prevent production of Abeta.”
References:
1. Hyang-Sook Hoe, et al. Georgetown University Medical Center.
