Protein kinases control the activity, structure and cellular localization of enzymes in eukaryotic cells by phosphorylation. The process of reversible phosphorylation allows proteins to quickly switch between active and inactive states, allowing the regulation of countless cellular processes. Substantial evidence implicates aberrant protein kinase signalling in AlzheimerÕs disease (AD). Neuroinflammation and synaptic failure are considered early events in the course of AD and are hence attractive targets for the prevention and pharmacological intervention to slow down or halter disease progression. Protein kinase profiling of 100 hippocampal post mortem brain tissue lysates of patients with AD and non-demented controls was performed using a peptide-based microarray platform. The results show an overall decrease of protein kinase activity, which correlates well with disease progression. The involvement of casein kinase 2 (CK2) in AD is far from clear. We find increased levels of CK2 in the hippocampus and temporal cortex of AD patients compared to non-demented controls. CK2 immunoreactivity is specifically increased in astrocytes that are associated with amyloid deposits, one of the hallmarks of AD. CK2 might be considered a potential drug target for the modulation of neuroinflammation in AD. The need for biomarkers that reflect early stages of AD pathology led us to explore the potential of using protein kinase activity profiling as a clinical biomarker for AD. We show that serine/threonine protein kinase activity is present in clinical CSF and that the activity is significantly lower in AD compared to controls.