F 4-neuroprostanes (F 4-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 (F 2-dihomo-IsoPs) that were 28 Da larger than but otherwise closely resembled F 2-isoprostanes (F 2-IsoPs), which are generated by free radical attack on ara-chidonic acid. Phospholipids derived from human cerebral gray matter, white matter, and myelin similarly oxidized ex vivo showed that the ratio of esterified F 2-dihomo-IsoPs to F 2-NeuroPs was ∼ 10-fold greater in myelin-derived than in gray matter-derived phospholipids. Finally, we showed that F 2-dihomo-IsoPs are significantly increased in white matter samples from patients with Alzheimer's disease.HB We pro pose that F 2-dihomo-IsoPs may serve as quantitative in vivo biomarkers of free radical damage to myelin from primate white matter.
- Alzheimer's disease brain lipids
ASJC Scopus subject areas
- Cell Biology