A growing body of evidence suggests a role for soluble alpha-amyloid precursor
protein (sAPPalpha) in pathomechanisms of Alzheimer disease (AD). This
cleavage product of APP was identified to have neurotrophic properties.
However, it remained enigmatic what proteins, targeted by sAPPalpha, might be
involved in such neuroprotective actions. Here, we used high-resolution two-
dimensional polyacrylamide gel electrophoresis to analyze proteome changes
downstream of sAPPalpha in neurons. We present evidence that sAPPalpha
regulates expression and activity of CDK5, a kinase that plays an important
role in AD pathology. We also identified the cytoprotective chaperone ORP150
to be induced by sAPPalpha as part of this protective response. Finally, we
present functional evidence that the sAPPalpha receptor SORLA is essential to
mediate such molecular functions of sAPPalpha in neurons