[Molecular mechanisms in Alzheimer disease]

With the aim of investigating the transport and metabolism of amyloid precursor protein (APP) in neurons, APP was expressed in neurons from the hippocampus using the Semliki-Forest virus vector. It was found that APP in the cell migrates from the nucleus into the axons and from there into the dendrites. During this migration, human APP is split at the total of six places, resulting in particular in the formation of beta A4 amyloid peptide. A greater production of beta A4 was observed in persons with inherited forms of Alzheimer's disease. In rat APP, in contrast, the amount of beta A4 secreted is clearly reduced. These findings suggest that beta A4 plays a central role in the genesis of the disease. The experimental methods open up the possibility of developing and testing therapeutic approaches to Alzheimer's disease.