Alzheimer's disease (AD) is characterized pathologically by selective neuronal loss and by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs). Since calcium/calmodulin-dependent protein kinase II-alpha (CaMKII-alpha), one of the most abundant kinases in the brain, is involved in the phosphorylation of tau and amyloid precursor protein (APP), we examined the expression of CaMKII-alpha and its relationships with the neuropathology in the hippocampus of AD patients using immunohistochemistry and double-labeling immunofluorescence methods. The results showed that CaMKII-alpha containing neurons were selectively lost in the CA1 subfield of AD hippocampus and accompanied with enhanced immunoreactivity in the remaining neurons. About 33% hyperphosphorylated tau-containing neurons labeled by monoclonal antibody AT-8 were also immunoreactive for CaMKII-alpha. Moreover, we found for the first time that the immunoreactivity of CaMKII-alpha was largely deposited in the SPs of the AD hippocampus. The pattern of the co-localization of CaMKII-alpha with beta amyloid depended on the type of SPs. Since the co-localization of CaMKII-alpha with hyperphosphorylated tau is relatively rare, we concluded that CaMKII-alpha may be related with beta-amyloid more closely than being involved in tau hyperphosphorylation.