Protein Linked to Alzheimer's Both Good and Bad

(Ivanhoe Newswire) -- New data about amyloid precursor protein, (APP), a protein implicated in the development of Alzheimer's disease (AD), suggests it also may have a positive role -- directly affecting learning and memory during brain development.

So is APP good or bad? Researchers at Georgetown University Medical Center say both, and that a balance of APP is critical.

AD, the fourth leading cause of death in the United States, is characterized by neuronal cell death and a progressive loss of brain function.

Abeta, one of many proteins associated with the disease and a known neurotoxin, is released when APP is cut by several enzymes. When Abeta is released, it can form plaque, a contributing factor in AD. In this way, Abeta and APP are involved in the early process of AD 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 in the cognitive decline seen in AD. Georgetown University Medical Center researchers say that while APP is negatively associated with AD, it appears to play a positive role in brain development.

In this new research, the GUMC scientists found decreased density of dendritic spines, the protrusions that allow communication between brain neurons, in mice that have been genetically modified not to produce APP.

The scientists then studied four-week-old mice that over-produced APP and found a significant increase in spine density. At one year old, however, these mice had Abeta plaques, as well as decreased spine density due to the neurotoxic effect of Abeta.

"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," study author Hyang-Sook Hoe, PhD, of the GUMC department of neuroscience, was quoted as saying. "One strategy to counteract development of Alzheimer's disease is to maintain balance in APP protein expression in order to prevent production of Abeta."

SOURCE: Presented at the annual meeting of the Society for Neuroscience, October 18, 2009

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