P2‐020: Lipidomic Profile of Human Cerebrospinal Fluid After an Intravenous Triglyceride Infusion
Year: 2019
Type: article
Abstract: High-fat diets are a risk factor for Alzheimer's disease, but little is known about the mechanisms. In addition, little is known about how lipids in the blood affect brain lipids. Here, we analyzed the lipidomic signature of cerebrospinal fluid (CSF) in older adults that received an intravenous infusion of triglycerides (TG). Older adults with Alzheimer's risk factors (n=21, age 67.7 ± 8.6, 38% APOE E4 carrier status) underwent a 5-hour TG or saline infusion followed 3 hours later by lumbar puncture for CSF collection on different days in crossover design. The infusion, Liposyn II, was comprised of 10% safflower oil and 10% soybean oil. Lipids in the CSF samples were extracted using dichloromethane/methanol after the addition of isotope labeled internal standards. Lipids were analyzed using the Lipidyzer platform consisting of an AB Sciex 5500 MS/MS system equipped with SelexION for differential mobility spectrometry. Multiple reaction monitoring was used to target and quantify lipids in both positive and negative ionization modes with and without differential mobility spectrometry. We detected around 200 lipids per sample with an average CV of 5.2% for lab QC technical replicates. The infusion increased the concentration of diacylglycerols (p=0.027) and lysophosphatidylcholines (LPC) (p=0.003) as a class, and reduced dihydroceramides (p=0.007). Participant characteristics of sex and cognitive diagnosis did not influence lipid class concentrations; however, E4 carriers had higher free fatty acids (p=0.031). Using MetaboAnalyst we identified 9 individual lipid species that changed with the infusion (paired t test, false discovery rate q < 0.1) and 4 of these species differed by E4 carrier status. Acute hyperlipidemia resulted in alterations in a limited number of specific classes of lipids in the CSF. APOE genotype further influenced lipid concentrations in both the fasted and hyperlipidemic state.
Source: Alzheimer s & Dementia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2980779429