Phosphorylation of the amyloid precursor protein (APP): Is this a mechanism in favor or against Alzheimer's disease?

This review discusses the phosphorylation of the Amyloid Precursor Protein (APP) and the possible role of this phosphorylation in Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques in the brain parenchyma and neurofibrillary tangles comprised of hyperphosphorylated tau. APP plays a primary role in the pathogenesis of AD, because its processing generates the amyloid beta peptide (Aβ), the core of the amyloid plaque. APP has a large N-terminal extracellular domain and a short intracellular C-terminal domain that can be phosphorylated by various protein kinases. This review summarized recent work describing the phsphorylation of APP and the downstream events induced by this phosphorylation as well as the impact of APP phosphorylation on APP function and on the production of Aβ peptide.