The expression of calcium/calmodulin-dependent protein kinase II-alpha 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-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.
Wang
Yue-Ju
YJ
Geriatric Department, the First Affiliated Hospital, Anhui Medical University, Hefei 230022, P.R. China.
Chen
Gui-Hai
GH
Hu
Xiang-You
XY
Lu
Ya-Ping
YP
Zhou
Jiang-Ning
JN
Liu
Rong-Yu
RY
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins; C517657:CAMK2A protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases