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.
McKee
A C
AC
Department of Neuropathology, Massachusetts General Hospital, Boston 02114.
Kosik
K S
KS
Kennedy
M B
MB
Kowall
N W
NW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009454:Neurofibrils / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000201:enzymology*; D011494:Protein Kinases / Q000032:analysis*; D016875:tau Proteins
D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases