title: The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer's disease.
abstract: 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.
authors.affiliation: Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. morley@slu.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Morley
authors.forename: Harvey James
authors.initials: HJ
authors.lastname: Armbrecht
authors.forename: Susan A
authors.initials: SA
authors.lastname: Farr
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Kumar
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D059165:Hormesis; D008550:Melatonin / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D016564:Amyloid beta-Protein Precursor; D008550:Melatonin