The expression of calcium/calmodulin-dependent protein kinase II-α in the hippocampus of patients with Alzheimer's disease and its links with AD-related pathology

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-α (CaMKII-α), 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-α and its relationships with the neuropathology in the hippocampus of AD patients using immunohistochemistry and double-labeling immunofluorescence methods. The results showed that CaMKII-α 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-α. Moreover, we found for the first time that the immunoreactivity of CaMKII-α was largely deposited in the SPs of the AD hippocampus. The pattern of the co-localization of CaMKII-α with beta amyloid depended on the type of SPs. Since the co-localization of CaMKII-α with hyperphosphorylated tau is relatively rare, we concluded that CaMKII-α may be related with β-amyloid more closely than being involved in tau hyperphosphorylation.