The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer's disease

The senescence accelerated mouse (SAMP8) is a spontaneous animal model of overproduction of amyloid precursor protein (APP) and oxidative damage. It develops early memory disturbances and changes in the blood–brain barrier resulting in decreased efflux of amyloid-β protein from the brain. It has a marked increase in oxidative stress in the brain. Pharmacological treatments that reduce oxidative stress improve memory. Treatments that reduce amyloid-β (antisense to APP and antibodies to amyloid-β) not only improve memory but reduce oxidative stress. Early changes in lipid peroxidative damage favor mitochondrial dysfunction as being a trigger for amyloid-β overproduction in this genetically susceptible mouse strain. This sets in motion a cycle where the increased amyloid-beta further damages mitochondria. We suggest that this should be termed the Inflammatory-Amyloid Cycle and may well be similar to the mechanisms responsible for the pathophysiology of Alzheimer's disease. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

► Oxidative damage to neuronal cells may influence the pathogenesis of Alzheimer's disease. ► SAMP8 mouse—an excellent model to study Aβ overproduction/oxidative damage to brain tissue. ► Aβ overproduction can trigger what becomes a vicious cycle. ► Mitochondrial dysfunction resulting in inflammation can result in a vicious cycle. ► Low dose Aβ—physiologically important to memory and protects neurons from oxidative damage.