Reduction of NR1 and phosphorylated Ca2+/calmodulin-dependent protein kinase II levels in Alzheimer's disease.

Ca 2+ influx through the N-methyl-D-aspartate-type glutamate receptor leads to activation and postsynaptic accumulation of Ca 2+ / calmodulin-dependent protein kinase II. NRI and NR2B subunits of N-methyl-D-aspartate receptor serve as high-affinity Ca 2+ /calmodulin-dependent protein kinase II docking sites in dendritic spines on autophosphorylation of Ca 2+ /calmodulin-dependent protein kinase II. By comparative Western blot analysis, we show a reduction of NRI and phosphorylated Ca 2+ /calmodulin-dependent protein kinase II levels in the frontal cortex and hippocampus of Alzheimer's disease brains. We also found a significant correlation between phosphorylated Ca 2+ /calmodulin-dependent protein kinase II and NRI levels. Our study extends the view that N-methyl-D-aspartate receptor deficiency underlies memory impairment in Alzheimer's disease, and that this process likely involves insufficient activation of Ca 2+ /calmodulin-dependent protein kinase II.