Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5

The mature form of Alzheimer's P-amyloid precursor protein (APP) is phospho rylated specifically at Thr(668) in neurons. In mature neurons, phosphoryla ted APP is detected in neurites, with dephosphorylated APP being found most ly in the cell body. In vitro, active cyclin-dependent kinase 5 (Cdk5) phos phorylated the cytoplasmic domain of APP at Thr(668). Treatment of mature n eurons with an antisense oligonucleotide to Cdk5 suppressed Cdk5 expression and significantly diminished the level of phosphorylated APP, The expressi on of APP was unaffected in antisense-treated neurons. These results indica te that in neurons APP is phosphorylated by Cdk5, and that this may play a role in its localization.