Brains of aged apolipoprotein E-deficient mice have increased levels of F-2-isoprostanes, in vivo markers of lipid peroxidation

Apolipoprotein E (apoE) is the major apolipoprotein of the CNS, Differentia l expression of apoE isoforms has been linked to longevity and to the patho genesis of Alzheimer's disease. Several studies have demonstrated that this glycoprotein is important in mature as well as in aging CNS, where it may serve neurotrophic and/or neuroprotective functions. Some reports have show n that apoE-deficient mice have age-dependent neurodegeneration and cogniti ve impairment; others have not confirmed these observations, ApoE-deficient mice also develop hypercholesterolemia on a chow diet and have in vivo inc reased plasma lipid peroxidation products. F-2-isoprostanes are prostagland in F-2 alpha isomers and chemically stable peroxidation products of arachid onic acid. Both isoprostane F-2 alpha-III and isoprostane F-2 alpha-VI were markedly elevated in the brains of aged apoE-deficient mice compared with either wild-type C57 Bl/6 mice or a distinct mouse model of hypercholestero lemia, the low-density lipoprotein receptor-deficient mouse. By contrast, n o difference in isoprostane levels was observed in young apoE-deficient mic e compared with age-matched wild-type control mice. Our findings indicate t hat disorder of lipid metabolism in the absence of apoE can induce an age-d ependent increase in brain lipid peroxidation products.