Increased Levels of 4-hydroxynonenal and Acrolein, Neurotoxic Markers of Lipid Peroxidation, in the Brain in Mild Cognitive Impairment and Early Alzheimer's Disease

Previous studies show increased levels of lipid peroxidation and neurotoxic by-products of lipid peroxidation including 4-hydroxynonenal (HNE) and acrolein in vulnerable regions of the Alzheimer's disease (AD) brain. To determine if lipid peroxidation occurs early in progression of AD, we analyzed levels of HNE and acrolein in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG) and cerebellum (CER) of 7 subjects with Mild Cognitive Impairment (MCI), six subjects with early AD (EAD) and sevem age-matched control subjects using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS). Our data show that there is a statistically significant (P<0.05) increase in HNE in HPG, SMTG and CER in MCI compared to age-matched control subjects. Specimens of SMTG also showed a significant increase in levels of acrolein in MCI. Comparison of EAD and control subjects showed a statistically significant increase in HNE in HPG and SMTG and a significant increase in acrolein in all three brain regions studied. We did not observe any statistically significant differences between MCI and EAD specimens. These results suggest that lipid peroxidation occurs early in the pathogenesis of AD.