Peripheral blood leukotriene B4 and E4 as biomarkers in Alzheimer’s disease

Abstract Background We showed recently that use of leukotriene receptor antagonists, typically used in asthma therapy, was associated with preserved executive function among people with Alzheimer’s disease (AD) dementia. The aim of this study was to determine if leukotriene B4 (LTB4) and E4 (LTE4) would be associated with longitudinal changes in cognitive performance and cerebrovascular disease markers in people with AD. Method Participants with clinical AD or mild cognitive impairment were identified from the Ontario Neurodegenerative Disease Research Initiative. LTB4 and LTE4 were extracted from fasting serum and quantified using ultra‐high performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Concentrations below the limit of detection were imputed using quantile regression imputation of left‐censored data. Cognition was assessed using composite scores for executive function (Trails Making Test B, Symbol Digit Modalities Test, Stroop switching task, and verbal fluency) and memory (Rey Auditory Verbal Learning Test and Brief Visuospatial Memory Test). White matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS) were quantified using T2‐weighted structural magnetic resonance imaging (MRI). Longitudinal associations between baseline LTB4 or LTE4 and cognition and imaging markers at baseline and 1‐year‐follow‐up were assessed using mixed‐effects linear regression models, controlling for baseline demographic factors, medication use, and vascular comorbidities. Findings were corrected for multiple comparisons using a 5% false discovery rate. Result Among 158 participants (mean age = 69.22 years, 51% female, mean education = 14.61 years), higher baseline concentrations of LTB4 were not associated with performance in executive function or memory over time nor with changes in WMH, lacunes, or PVS over time. Higher baseline concentrations of LTE4 were associated with better performance in memory over time (β = 0.153 [95% CI = 0.026, 0.287]; however, this finding did not survive correction for multiple comparisons (adjusted p = 0.260; Table 1). Conclusion In a group of patients with AD, higher LTB4 and LTE4 in serum were not associated with changes in cognitive performance nor markers of cerebrovascular disease. These findings suggest very little potential for serum leukotrienes as biomarkers for cognitive decline of cerebrovascular disease progression in AD.