P2‐209: High Concentrations of Antibodies Recognizing Egg‐albumin and Bovine Casein in the CSF of Patients With Severe Alzheimer's Disease

Abstract

Background: Neuroinflammation plays an essential role in the advancement of both Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD). Polyunsaturated fatty acids and their oxidized metabolites, in particular the bioactive oxylipins, are multifunctional molecules involved in the regulation and resolution of inflammation. The relationships between oxylipins, AD and SIVD remain to be clarified. Methods:The present study applied a targeted lipidomics platform to quantitatively probe for 72 oxylipins in AD (n¼30) and non-AD (n¼54) participants, including strata of extensive (n¼43, SIVD) or minimal (n¼41, Non-SIVD) white matter hyperintensities (WMHs). WMHs were identified through multimodal MRI, and quantified using a personalized semi-automatic processing pipeline (Lesion Explorer). The oxylipins were extracted from serum using solid phase extraction, and quantified with UPLC-MS/MS. Executive function was assessed using the Stroop and Trail-Making B (TMT-B) tests. Results: In a multivariate analysis of covariance model controlling for age and sex, the lipoxygenase (LOX)-derived dihomo-gamma-linoleic acid metabolite, 15(s)-hydroxyeicosatrienoic acid (15(s)-HETrE; detectable in n¼81) was lower in SIVD (F 1,80 ¼11.51, p¼0.001) but not AD (F 1,80 ¼2.74, p¼0.102). The LOX derived arachidonic acid metabolite, 15-hydroxyeicosatetraenoic acid (15-HETE; detectable in n¼65), was lower in AD (F 1,64 ¼4.98, p¼0.032) but not SIVD (F 1,64 ¼0.05, p¼0.821). In participants with extensive SIVD but no AD (n¼28), two LOX derived linoleic acid metabolites, 9-hydroxyoctadecadienoic acid (9-HODE) and 13-HODE, were found to be positively associated with Z-scores on the Stroop (r¼0.523, p¼0.004 and r¼0.444, p¼0.018, respectively) and p¼0.001 and r¼0.557, p¼0.003, respectively), and negatively associated with periventricular WMH volume (r¼-0.386, p¼0.042; r¼-0.393, p¼0.039, respectively). Conclusions:The generation of LOX metabolites may be compromised differently in AD and SIVD. These metabolites might be protective against white matter injury and cognitive decline caused by subcortical ischemic vascular disease.