Assessment of Lipid Peroxidation in Alzheimer’s Disease Differential Diagnosis and Prognosis

Abstract

Alzheimer’s disease (AD) and other dementias are becoming increasingly common in the older population, and the number of people affected is expected to increase in a few years. Nowadays, biomarkers used in early AD diagnosis are expensive and invasive. Therefore, this research field is growing. In fact, peroxidation by-products derived from the oxidation of brain lipids (arachidonic (AA), docosahexanoic (DHA) and adrenic acid (AdA)) could be potential biomarkers, participating in the mechanisms of inflammation, neurotoxicity and cell death in AD pathology. Previous studies have shown specificity between lipid peroxidation compounds and other dementias (e.g., Lewy bodies (DLB), frontotemporal dementia (FTD)), but more research is required. Lipid peroxidation compounds (prostaglandins, isoprostanes, isofurans, neuroprostanes, neurofurans, dihomo-isoprostanes and dihomo-isofurans) were analysed by liquid chromatography and mass spectrometry in plasma samples from participants classified into a healthy group (n = 80), a mild cognitive impairment due to AD group (n = 106), a mild dementia due to AD group (n = 70), an advanced dementia due to AD group (n = 11) and a group of other non-AD dementias (n = 20). Most of these compounds showed statistically significant differences between groups (p < 0.05), showing higher levels for the healthy and non-AD groups than the AD groups. Then, a multivariate analysis was carried out on these compounds, showing good diagnosis indexes (AUC 0.77, sensitivity 81.3%, positive predictive value 81%). Moreover, evaluating AD disease prognosis, two compounds (15-F2t-IsoP and 14(RS)-14-F4t-NeuroP) and three total parameters (isoprostanes, isofurans and neurofurans) showed significant differences among groups. Some compounds derived from the oxidation of AA, DHA and AdA have demonstrated their potential use in differential AD diagnosis. Specifically, 15-F2t-IsoP, 14(RS)-14-F4t-NeuroP and the total parameters for isoprostanes, isofurans and neurofurans have shown prognostic value for AD from its earliest stages to its most severe form.