Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration.
Cyclin-dependent kinase 5 (cdk5) is one of the candidate kinases involved in the abnormal hyperphosphorylation of tau. To have a direct effect on tau hyperphosphorylation, cdk5 protein levels and enzyme activity should be upregulated in especially those neurons that develop neurofibrillary tangles (NFTs). We studied the distribution of cdk5 immunoreactivity in neurons with or without early- and late-stage NFTs in hippocampal, entorhinal, transentorhinal, temporal and frontal cortices, and cerebellum of Alzheimer's disease (AD) and control brain. The immunocytochemical localisation of cdk5 was compared with that obtained using antibodies to PHF-tau (tau in paired helical filaments of NFTs, mAb AT8) and ubiquitin as markers of early and late stage NFTs, respectively. Immunoreactivities of cdk5 and PHF-tau were found in neuronal perikarya and processes of hippocampal, entorhinal, transentorhinal, temporal and frontal, and cerebellar cortices. An apparent increase of cdk5 immunoreactivity was seen in pretangle neurons and in neurons bearing early stage NFTs. These findings suggest that this kinase might be involved in the formation of NFTs at a relatively early stage in the neocortex.
Pei
J J
JJ
Section for Geriatric Medicine, Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Novum, KFC, S-141 86, Huddinge, Sweden.
Grundke-Iqbal
I
I
Iqbal
K
K
Bogdanovic
N
N
Winblad
B
B
Cowburn
R F
RF
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D038362:Glycogen Synthase Kinase 3; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000201:enzymology*; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000201:enzymology*; D009474:Neurons / Q000737:chemistry / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D013702:Temporal Lobe / Q000201:enzymology; D016875:tau Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3