NEW YORK (Reuters Health) – By studying fruit flies, Belgian investigators have discovered that the normal function of the amyloid precursor protein (APP), which has been implicated in Alzheimer‘s disease, is to stimulate the growth of nerve paths in the brain. This may aid in recovery after brain injury, but may also contribute to the development of Alzheimer’s disease.
"In an ironic twist of evolution," lead investigator Dr. Bassem A. Hassan told Reuters Health, "a protective protein, which probably allows the brain to survive and function robustly as we go through the stressful, productive phases of our lives, produces, as an inevitable consequence of its necessary function, a toxic peptide that impairs us in old age."
The normal function of APP, one of the most important proteins related to Alzheimer’s disease and the protein that gives rise to amyloid-beta, has been unclear, Hassan from the Flanders Interuniversity Institute for Biotechnology in Leuven and colleagues point out in the EMBO Journal, the journal of the European Molecular Biology Organization.
To investigate, Hassan and his colleagues conducted a series of studies in the brains of fruit flies. The researchers found that human APP and its fruit fly counterpart, APPL, promoted nerve cell branching in the brains of mature fruit flies. Brain injury in the fruit fly stimulated APPL in nerve cells – and fruit flies genetically engineered to lack APPL showed increased mortality after traumatic brain injury.
Dr. Hassan said that it appears, at least in fruit flies, "that a pathway triggered by APP may be able to induce re-growth of injured (nerve cell) connections. If the same is true in mammals, then turning on that pathway may one day provide a way of restoring the connection of severed nerves."
The findings may also have implications in the understanding of some aspects of the development of Alzheimer’s disease, as well as the link between traumatic brain injury and Alzheimer’s disease.
Studies have shown that head trauma can increase one’s chances of developing Alzheimer’s disease. This might be explained by the fact that "APP, the central protein in Alzheimer’s disease, is a trauma response factor," Hassan said.
He and colleagues hypothesize that during adult life stressful or traumatic events in the brain lead to APP upregulation and as a side effect of this, amyloid-beta peptides are generated, which may eventually disrupt neuronal connections, and lead to Alzheimer’s disease.
EMBO Journal, July 2005.
By Megan Rauscher
