Neuronal and vascular oxidative stress in Alzheimer's disease

The brain is a highly metabolically active organ producing large amounts of reactive oxygen species (ROS). These ROS are kept in check by an elaborate network of antioxidants. Although ROS are necessary for signaling and synaptic plasticity, their uncontrolled levels cause oxidation of essential macromolecules such as membrane lipids, nucleic acids, enzymes and cytoskeletal proteins. Indeed, overproduction of ROS and/or failure of the antioxidant network lead to neuronal oxidative stress, a condition associated with not only aging but also Alzheimer's disease (AD). However, the specific source of excessive ROS production has not yet been identified. On one hand, amyloid beta (Aβ) has been extensively shown to act as an oxidant molecule. On the other hand, oxidative stress has been shown to precede and exacerbate Aβ pathology. This review will address the involvement of oxidative stress in the context of neuronal as well as vascular dysfunction associated with AD.