Abstract
Unlike F4-neuroprostanes (F4-NeuroPs), which are relatively selective in vivo markers of oxidative damage to neuronal membranes, there currently is no method to assess the extent of free radical damage to myelin with relative selectively. The polyunsaturated fatty acid adrenic acid (AdA) is susceptible to free radical attack and, at least in primates, is concentrated in myelin within white matter. Here, we characterized oxidation products of AdA as potential markers of free radical damage to myelin in human brain. Unesterified AdA was reacted with a free radical initiator to yield products (F2-dihomo-IsoPs) that were 28 Da larger than but otherwise closely resembled F2-isoprostanes (F2-IsoPs), which are generated by free radical attack on arachidonic acid. Phospholipids derived from human cerebral gray matter, white matter, and myelin similarly oxidized ex vivo showed that the ratio of esterified F2-dihomo-IsoPs to F4-NeuroPs was approximately 10-fold greater in myelin-derived than in gray matter-derived phospholipids. Finally, we showed that F2-dihomo-IsoPs are significantly increased in white matter samples from patients with Alzheimer's disease. We propose that F2-dihomo-IsoPs may serve as quantitative in vivo biomarkers of free radical damage to myelin from primate white matter.