Enhanced brain levels of 8,12-iso-iPF2α-VI differentiate AD from frontotemporal dementia

Objective: To quantify the isoprostane 8,12-iso-iPF(2alpha)-VI in brain tissues obtained from patients with AD, patients with frontotemporal dementia (FTD), and controls. Background: Enhanced brain oxidative stress with secondary damage to cellular macromolecules may play a role in the pathogenesis of AD and FTD. The isoprostane 8,12-iso-iPF(2alpha)-VI is a specific and sensitive marker of in vivo lipid peroxidation and is increased in AD. Methods: Levels of this isoprostane were determined by gas chromatography/negative ion chemical ionization mass spectrometry. Results: Levels of 8,12-iso-iPF(2alpha)-VI were markedly elevated in both frontal and temporal cortex of AD brains compared to the corresponding areas of FTD and controls. No significant difference in brain 8,12-iso-iPF(2alpha)-VI levels for any regions considered was observed between FTD and controls. Conclusions: Lipid peroxidation is a feature of AD, but not FTD. The generation of 8,12-iso-iPF(2alpha)-VI in the brain is not a general or final common pathway of neurodegeneration, but may be relatively specific for disease processes in AD and not FTD.