Abbreviations used : AD, Alzheimer's disease ; CBL, cerebellar hemisphere ; HPG, hippocampus and parahippocampal gyrus ; IPL, inferior parietal lobule ; PMI, postmortem interval ; OCC, occipital areas 17, 18 ; SMT, superior and middle temporal gyri.
Impaired Proteasome Function in Alzheimer's Disease
Article first published online: 25 DEC 2001
Journal of Neurochemistry
Volume 75, Issue 1, pages 436–439, July 2000
How to Cite
Keller, J. N., Hanni, K. B. and Markesbery, W. R. (2000), Impaired Proteasome Function in Alzheimer's Disease. Journal of Neurochemistry, 75: 436–439. doi: 10.1046/j.1471-4159.2000.0750436.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Alzheimer's disease;
- Amyloid β-peptide;
- Oxidative stress;
Abstract : Inhibition of proteasome activity is sufficient to induce neuron degeneration and death ; however, altered proteasome activity in a neurodegenerative disorder has not been demonstrated. In the present study, we analyzed proteasome activity in short-postmortem-interval autopsied brains from 16 Alzheimer's disease (AD) and nine age- and sex-matched controls. A significant decrease in proteasome activity was observed in the hippocampus and parahippocampal gyrus (48%), superior and middle temporal gyri (38%), and inferior parietal lobule (28%) of AD patients compared with controls. In contrast, no significant decrease in proteasome activity was observed in either the occipital lobe or the cerebellum. The loss of proteasome activity was not associated with a decrease in proteasome expression, suggesting that the proteasome may become inhibited in AD by a posttranslational modification. Together, these data indicate a possible role for proteasome inhibition in the neurodegeneration associated with AD.