Abstract
Alzheimer's disease (AD) is a progressive and devastating disorder that is often preceded by mild cognitive impairment (MCI). In the present study, we report that in multiple cortical areas of MCI and AD subjects, there is a significant impairment in ribosome function that is not observed in the cerebellum of the same subjects. The impairment in ribosome function is associated with a decreased rate and capacity for protein synthesis, decreased ribosomal RNA and tRNA levels, and increased RNA oxidation. No alteration in the level of initiation factors was observed in the brain regions exhibiting impairments in protein synthesis. Together, these data indicate for the first time that impairments in protein synthesis may be one of the earliest neurochemical alterations in AD and directly demonstrate that the polyribosome complex is adversely affected early in the development of AD. These data have important implications for AD studies involving proteomics and studies analyzing proteolysis in AD, indicate that oxidative damage may contribute to decreased protein synthesis, and suggest a role for alterations in protein synthesis as a novel contributor to the onset and development of AD.
References
31
Referenced
373
{'key': '2023041303150484000_25.40.9171.1', 'first-page': '2203', 'volume': '12', 'year': '1992', 'journal-title': 'Mol Cell Biol'}
/ Mol Cell Biol (1992)10.1016/S0002-9440(10)63687-5
10.1007/BF00308809
10.1097/00001756-200212200-00011
10.1007/BF00966123
10.1046/j.1532-5415.5157.x
10.1074/jbc.M107706200
10.1111/j.1471-4159.2004.02802.x
10.1046/j.1365-2990.2002.t01-1-00410.x
/ Neuropathol Appl Neurobiol (2002)10.1212/WNL.41.7.1006
/ Neurology (1991)10.1016/S0378-1119(03)00629-2
10.1016/j.yexcr.2004.03.016
10.1016/S0006-291X(03)00485-6
10.1128/MCB.23.24.9251-9261.2003
10.1074/jbc.M500526200
10.1212/01.WNL.0000156156.13641.BA
/ Neurology (2005)10.1016/0169-328X(89)90060-0
/ Mol Brain Res (1989)10.1097/00001756-200410050-00019
10.1212/01.WNL.0000080366.90234.7F
/ Neurology (2003)10.1001/archneur.58.3.397
10.1523/JNEUROSCI.19-06-01959.1999
/ J Neurosci (1999)10.1038/sj.emboj.7600049
10.1016/S0969-9961(03)00086-X
{'key': '2023041303150484000_25.40.9171.24', 'first-page': '65', 'volume': '9', 'year': '1997', 'journal-title': 'Int Psychogeriatr'}
/ Int Psychogeriatr (1997)10.1001/archneur.56.3.303
10.1002/ana.10161
10.1126/science.6206567
10.1212/WNL.49.6.1498
/ Neurology (1997)10.1016/S0962-8924(03)00054-0
10.1093/jb/mvh001
10.1016/S0070-2137(96)80004-5
Dates
Type | When |
---|---|
Created | 19 years, 10 months ago (Oct. 5, 2005, 5:37 p.m.) |
Deposited | 2 years, 4 months ago (April 13, 2023, 12:59 p.m.) |
Indexed | 14 hours, 47 minutes ago (Sept. 3, 2025, 6:49 a.m.) |
Issued | 19 years, 10 months ago (Oct. 5, 2005) |
Published | 19 years, 10 months ago (Oct. 5, 2005) |
Published Online | 19 years, 10 months ago (Oct. 5, 2005) |
Published Print | 19 years, 10 months ago (Oct. 5, 2005) |
@article{Ding_2005, title={Ribosome Dysfunction Is an Early Event in Alzheimer’s Disease}, volume={25}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.3040-05.2005}, DOI={10.1523/jneurosci.3040-05.2005}, number={40}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Ding, Qunxing and Markesbery, William R. and Chen, Qinghua and Li, Feng and Keller, Jeffrey N.}, year={2005}, month=oct, pages={9171–9175} }