In situ hybridization of calcium/calmodulin dependent protein kinase II and tau mRNAs; species differences and relative preservation in Alzheimer's disease.
Abnormal phosphorylation of the microtubule associated protein tau component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) may result from alterations in protein kinase expression. Calcium/calmodulin dependent protein kinase II (CaM kinase II) has been shown to phosphorylate tau in vitro in such a way to decrease its electrophoretic mobility. A68, apparently a modified form of tau in AD brain, also shows abnormal phosphorylation and slower mobility than tau. To further examine the role of CaM kinase II in AD, in situ hybridization studies were performed on tissues from rat, monkey and human to examine and compare the patterns of CaM kinase II mRNA expression in different brain regions. The most notable differences among the three species were observed in dendrites in layer I of isocortex, in the molecular layer of the dentate gyrus and stratum radiatum and stratum lacunosum-moleculare in hippocampus, where hybridization was detected in rat, but not in monkey or human brain. In addition, comparisons between tau and CaM kinase II mRNA expression were made in tissue from normal aged adults and AD patients, especially in areas prone to NFT formation. CaM kinase II and tau mRNAs were co-expressed in many neuronal populations, both those which are prone to NFT formation as well as those which are rarely affected by AD changes. No major differences in the relative abundance of either CaM kinase II or tau mRNA within particular neuronal populations was noted between normal aged and AD brain. Diminished hybridization was associated with serve neuronal pathology and cell loss.
Mah
V H
VH
Department of Neurobiology and Anatomy, University of Rochester Medical Center, NY 14642.
Eskin
T A
TA
Kazee
A M
AM
Lapham
L
L
Higgins
G A
GA
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015342:DNA Probes; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D015342:DNA Probes; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D016875:tau Proteins; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases