Altered cerebrospinal fluid lipids in preclinical Alzheimer’s disease (651.6)

Abstract

Background and Objective: Although lipids constitute a major portion of the brain, preclinical changes in lipid metabolism in cerebrospinal fluids (CSF) have not been determined in sporadic Alzheimer’s disease (AD). Our objective is to test the hypothesis that altered brain lipid metabolism precedes AD clinical symptoms.Methods: We fractionated CSF into a 200,000 g supernatant fluid (SF) and nanoparticles (NP) fractions and used liquid chromatography tandem mass spectrometry to determine the glycerophospholipid (GP) and sphingolipid (SP) composition of these fractions from cognitively healthy (CH) subjects. We further analyzed lipids in subgroups of CH participants with normal beta amyloid to total Tau (Aβ/Tau) (CH_NAT) or with preclinical AD‐like Aβ/Tau pathology (CH_PAT), and in AD study participants.Results: Levels of some GP classes and species are higher in the SF fraction from CH_PAT compared with CH_NAT. In contrast, levels of some SP classes and species are higher in the NP fractions from CH_PAT compared with CH_NAT. Activity of metabolic enzymes, PLA2 and acid SMase are significantly altered in AD compared with both CH subgroups.Conclusions: Differences between CH_NAT and CH_PAT suggest increased turnover or remodeling of GP in brain interstitial fluid and SP in brain membrane‐derived lipids in preclinical AD. Means of regulating these lipid metabolic pathways may be beneficial in AD prevention.Grant Funding Source: L.K. Whittier and the Helen Posthuma Foundations