期刊
BRAIN PATHOLOGY
卷 20, 期 1, 页码 222-233出版社
WILEY
DOI: 10.1111/j.1750-3639.2009.00266.x
关键词
Alzheimer disease stage I; II; ATP-synthase alpha chain; entorhinal cortex; lipid peroxidation; oxidative stress
资金
- Spanish Ministry of Health, Instituto de Salud Carlos III FIS [PI05/1570, PI05/2214, PI08/0582]
- European Commission [LSHM-CT-2004-503039]
- Spanish Ministry of Education and Science [BFU2006-14495/BFI]
- Spanish Ministry of Health [RD06/0013/0012]
- Generalitat of Catalunya [2005SGR00101]
- La Caixa Foundation
Oxidative stress has been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Several proteins have been identified as targets of oxidative damage in AD dementia (usually stages V/VI of Braak) and in subjects with mild cognitive impairment associated with middle stages of AD pathology (stage IV of Braak). In this study, we investigate whether brain proteins are locally modified by oxidative stress at the first stages of AD-related pathology when morphological lesions are restricted to the entorhinal and transentorhinal cortices of neurofibrillary pathology (stages I/II of Braak). Using a proteomic approach, we show that the alpha subunit of the mitochondrial adenosine triphosphate (ATP)-synthase is distinctly lipoxidized in the entorhinal cortex at Braak stages I/II compared with age-matched controls. In addition, ATP-synthase activity is significantly lower in Braak stages I/II than age-matched control, while electron transport chain, expressed by the mitochondrial complex I activity, remains not affected. This is the first study showing oxidative damage in the first stage, and clinically silent period, of AD-related pathology characterized by entorhinal and transentorhinal tauopathy.
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