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INTRODUCTION: Altered regulation of lipid metabolism in Alzheimer disease (AD) can be characterized using lipidomic profiling. METHOD: 341 serum lipids were measured in 806 participants enrolled in the Alzheimer Disease Neuroimaging Initiative Phase 1 (ADNI1) cohort and analysed using lipid regression models and lipid set enrichment statistics. RESULTS: AD diagnosis was associated with 7 of 28 lipid sets of which four also correlated with cognitive decline, including polyunsaturated fatty acids. CSF amyloid beta Aβ1-42 correlated with glucosylceramides, lysophosphatidyl cholines and unsaturated triacylglycerides; CSF total tau and brain atrophy correlated with monounsaturated sphingomyelins and ceramides, in addition to EPA-containing lipids. DISCUSSION: Lipid desaturation, elongation and acyl chain remodeling are dysregulated across the spectrum of AD pathogenesis. Monounsaturated lipids were important in early stages of AD, while polyunsaturated lipid metabolism was associated with later stages of AD.

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