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Thus, although the EC from the aged female APOE4 mice did not require as much compensatory activity in its Complex I-mediated mitochondrial respiration as what we observed in the aged male APOE4 mice, it is possible that the presence of a compensatory effect in Complex I-mediated respiration in the EC of aged female APOE4 mice, in combination with an overall increase in ROS production throughout the brain of these mice resulting from the increased Complex II-mediated respiration, may lead to even greater pathogenic effects in the EC of aged female vs

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Until more definitive data emerge, it is prudent to prioritize pharmacologic therapies and to counsel patients that long-term supplement regimens entail uncertain benefits and costs

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