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Regional Expression of Key Cell Cycle Proteins in Brain from Subjects with Amnestic Mild Cognitive Impairment

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Abstract

Mild cognitive impairment (MCI) is regarded as a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer’s disease (AD). Previous studies had demonstrated increased expression of cell cycle proteins in AD brain. In the present study, we have analyzed the expression of the cell cycle proteins, CDK2, CDK5 and cyclin G1 in hippocampus and inferior parietal lobule (IPL) in subjects with amnestic mild cognitive impairment and control using Western blot analysis. The expression of CDK2, CDK5 and cyclin G1 were found to be significantly increased in MCI hippocampus as well as in IPL compared to control brain. These results suggest that some cells may have re-entered the cell cycle. However, the expression of CDK2 and CDK5 is greater in MCI hippocampus compared to those of MCI IPL, and hippocampus is a region that is severely affected by AD pathology. Since these proteins are involved directly or indirectly in microtubule destabilization and hyperphosphorylation of tau, and also in APP processing we hypothesize that cell cycle disturbance may be important contributor in the pathogenesis of AD.

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Acknowledgments

The authors would like to thank the University of Kentucky ADC Clinical Neuropathology Core faculty for providing the brain tissue used for this study. We thank Dr. Carlos F. de Mello for useful discussions. This work was supported in part by NIH grants to D.A.B. [AG-05119; AG-10836].

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Correspondence to D. Allan Butterfield.

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Special issue dedicated to Dr. John P. Blass.

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Sultana, R., Butterfield, D.A. Regional Expression of Key Cell Cycle Proteins in Brain from Subjects with Amnestic Mild Cognitive Impairment. Neurochem Res 32, 655–662 (2007). https://doi.org/10.1007/s11064-006-9123-x

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