Hippocampal Neurons Predisposed to Neurofibrillary Tangle Formation Are Enriched in Type II Calcium/Calmodulin-Dependent Protein Kinase
The microtubule-associated phosphoprotein, tau, is an integral component of paired helical filaments in Alzheimer neurofibrillary tangles (NFT). The mechanism of NFT formation is unknown but aberrant phosphorylation of tau may be contributory. Calcium/calmodulin-dependent protein kinase type II (CaM kinase II), the most abundant kinase in the brain, phosphorylates tau in vitro. We found CaM kinase II immunoreactivity concentrated in human hippocampal pyramidal neurons of CA1 and the subiculum. In Alzheimer's disease (AD) staining intensity of CA1 and subicular neurons is strikingly increased despite NFT formation and neuronal depletion. Enhanced CaM kinase II activity, possibly a result of deafferentation, may contribute to phosphorylation of tau protein leading to NFT deposition and neuronal death in AD.
© 1990 American Association of Neuropathologists, Inc. Received 20 September 1988; Accepted 27 June 1989. Supported in part by NIH grant AG05134 and AG06601, Massachusetts Alzheimer's Disease Research Center and NINDS Career Investigator Development Award (ACMcK) NS 01368-01. We thank Lawrence Cherkas for photographic assistance.