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Aberrant casein kinase II in Alzheimer's disease
D S Iimoto1, E Masliah, R DeTeresa
1University of California, San Diego, School of Medicine, La Jolla, CA 92093.
Abstract:
Abnormal protein phosphorylation has been identified in Alzheimer's disease (AD) for several proteins including a Mr 60,000 protein, a Mr 86,000 protein and a microtubule-associated protein tau. The Mr 86,000 protein is phosphorylated by protein kinase C, whereas protein kinases responsible for other aberrant phosphorylation reactions are not known. In addition to protein kinase C, another kinase, casein kinase II (CK-II), has now been shown to be aberrant in AD. The spermine-dependent CK-II activity is reduced by 84% in AD and the amount of CK-II as determined by its immunoreactivity on a Western blot is reduced by 63%. Furthermore, the distribution of CK-II in AD is altered. Although the neuronal cell body reacts well with CK-II antisera in the normal cortex, the non-tangle-bearing neurons in the AD cortex showed a 15-30% decrease in anti-CK-II immunoreactivity. The neurofibrillary tangles, on the other hand, stain very strongly with rabbit anti-CK-II and indicates that CK-II may be involved in the pathology of AD. The study of CK-II immunoreactivity for dementing diseases other than AD revealed a similar reduction, suggesting the CK-II involvement in the common process of neurodegeneration.
Insights
Casein kinase II (CK-II) activity and levels are significantly reduced in Alzheimer's disease (AD) brains. Altered CK-II distribution, particularly in neurofibrillary tangles, suggests its involvement in neurodegeneration common to dementing diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Abnormal protein phosphorylation is a hallmark of Alzheimer's disease (AD).
- Specific kinases responsible for aberrant phosphorylation in AD remain largely unknown.
- Protein kinase C is known to phosphorylate one abnormal protein in AD.
Purpose of the Study:
- To investigate the role of casein kinase II (CK-II) in Alzheimer's disease pathology.
- To quantify changes in CK-II activity and levels in AD brains.
- To examine the distribution of CK-II in relation to AD neuropathology.
Main Methods:
- Western blot analysis to determine CK-II protein levels.
- Measurement of spermine-dependent CK-II enzyme activity.
- Immunohistochemical staining using CK-II antisera on brain tissue.
Main Results:
- CK-II activity was reduced by 84% in AD brains.
- CK-II protein levels, assessed by immunoreactivity, decreased by 63% in AD.
- CK-II distribution was altered, with reduced immunoreactivity in non-tangle-bearing neurons and strong staining in neurofibrillary tangles.
Conclusions:
- Casein kinase II (CK-II) is aberrantly expressed and distributed in Alzheimer's disease.
- Reduced CK-II may contribute to the neurodegenerative processes observed in AD.
- Similar CK-II alterations in other dementing diseases suggest a common role in neurodegeneration.