Open AccessMitochondrial ATP‐Synthase in the Entorhinal Cortex Is a Target of Oxidative Stress at Stages I/II of Alzheimer's Disease Pathology
Author(s) -
Terni Beatrice,
Boada Jordi,
PorteroOtin Manuel,
Pamplona Reinald,
Ferrer Isidro
Publication year - 2010
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2009.00266.x
Subject(s) - tauopathy , entorhinal cortex , oxidative stress , pathology , alzheimer's disease , oxidative phosphorylation , mitochondrion , atp synthase , dementia , neuroscience , neurodegeneration , biology , hippocampus , disease , medicine , endocrinology , biochemistry , enzyme
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 α 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.