Localization and expression of cdc2 and cdk4 in Alzheimer brain tissue.
Two regulators of the eukaryotic cell cycle, cell division cycle 2 (cdc2) and cyclin-dependent kinase 4 (cdk4), have been reported to be related to Alzheimer's disease (AD) pathology, and especially to hyperphosphorylated tau protein. Using well-characterized polyclonal antibodies which recognize the C termini of cdc2 kinase and cdk4, we examined by immunohistochemistry brain tissues from patients with non-neurological conditions, AD and cerebral infarction. Semiquantitative mRNA analysis by RT-PCR was also done using non-neurological and AD brains. In AD, as previously reported, the antibody to cdc2 showed positive staining of a few intracytoplasmic neurofibrillary tangles (NFTs). In addition, this antibody gave positive immunolabelling in astrocytes and capillaries in all brains studied. In both AD and cerebral infarct cases, the staining of astrocytes was more intense than in non-neurological brain tissue. In all cases, the antibodies to cdk4 showed positive immunolabelling in the nuclei of all cell types except neurons. In AD tissue, the antibody showed additional staining of neuronal nuclei and cytoplasm. In contrast to a previous report, we did not find positive labelling of NFTs with the anti-cdk4 antibody. In infarct areas, particularly strong nuclear staining in glial cells was seen. The relative levels of cdk4 mRNA in AD brains were higher than those in controls. These data suggest that cdc2 kinase appears in glial cells capable of cell division and may play a role in the regulation of amyloid precursor protein processing and NFT formation in neurons. As suggested in a report on rat brain, neuronal expression of cdk4 may reflect some pathological process in damaged cells in AD.
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000906:Antibodies / Q000276:immunology; D001253:Astrocytes / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics* / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018816:Genes, cdc / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010766:Phosphorylation; D010770:Phosphotransferases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction