Amyloid beta-peptide effects on synaptosomes from apolipoprotein E-deficient mice

Apolipoprotein E (apoE) is present in the brain and may contribute to neuro physiologic or neuropathologic events, depending on environmental and genet ic influences. Recent studies indicate a role for apoE in synaptic plastici ty and maintenance of synaptic membrane symmetry, suggesting that apoE may be involved in regulating synaptic homeostasis. In the present study, cereb rocortical synaptosomes were prepared from transgenic mice lacking apoE (ap oE KO) to analyze the possible contribution of apoE toward maintaining home ostasis in synaptosomes. Synaptosomal preparations from apoE KO and wild-ty pe mice exhibited similar basal levels of reactive oxygen species, mitochon drial function, and caspase activity; however, following application of amy loid beta-peptide [A beta(1-40)], apoE KO synaptosomes displayed increased levels of oxidative stress, mitochondrial dysfunction, and caspase activati on compared with synaptosomes from wild-type mice. Synaptosomal membranes f rom apoE KO mice were more fluid than wild-type synaptosomes and contained higher levels of thiobarbituric acid-reactive substances, consistent with e levated levels of lipid peroxidation occurring in the synapses of apoE KO m ice. Together, these data are consistent with a role for apoE in maintainin g homeostasis by attenuating oxidative stress, caspase activation, and mito chondrial homeostasis in synapses.