Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study

Abstract

Human apoE exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the gene. Total plasma apoE concentrations are closely related to these isoforms, but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used LC-MS/MS to discriminate between isoforms by identifying specific peptide sequences in subjects (three E2/E3, three E3/E3, and three E3/E4 phenotypes) who received a primed constant infusion ofH-leucine for 14 h. apoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates (PRs), but apoE2 catabolic rates and apoE4 PRs were lower. The mechanisms leading to the difference in total plasma apoE concentrations are therefore related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. On these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted.

Simple and Fast Assay for Apolipoprotein E Phenotyping and Glycotyping: Discovering Isoform-Specific Glycosylation in Plasma and Cerebrospinal Fluid

“…The ratios of E4/E2 and E4/E3 were also increased: for E4/E2 2.55 ± 0.07 in CSF and 0.73 ± 0.12 in plasma (p < 0.05); while for E4/E3, 1.51 ± 0.09 in CSF and 1.23 ± 0.18 in plasma (p = 0.06). These tissue-specific isoform ratios differences are consistent with previous studies [35][36][37]. They reflect the distinct metabolism of the apoE isoforms in the central nervous system and the periphery, as apoE does not cross the BBB [30], and its concentration in CSF is approximately ten-times lower than that in plasma [31].…”

“…First, the ratios of apoE isoforms differed in CSF from plasma, reflecting two distinct pools (brain and systemic) of apoE with different metabolic fates. In plasma, apoE2 had a larger relative abundance compared to apoE3; these findings are consistent with a lower fractional catabolic rate of apoE2 compared to apoE3 or apoE4 in plasma [37]. These isoform differences were not evident in CSF.…”

Spirulina Liquid Extract Protects against Fibrosis Related to Non-Alcoholic Steatohepatitis and Increases Ursodeoxycholic Acid

“…Isolation of lipoproteins was performed by fast protein liquid chromatography (ÄKTAFPLC) (GE Healthcare, Buc, France) using 200µL of plasma [16]. Plasma apolipoproteins (ApoA-I, ApoB100, ApoC-II, ApoC-III, and ApoE) were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) as previously described [17] with slight modifications due to specific mouse isoforms (Table S3). Gallbladder bile acids (BA) were further analyzed by LC-MS/MS as recently published [18].…”

APOE Alleles and Diet in Brain Aging and Alzheimer’s Disease

“…A major mechanism for hypercholesterolemia with APOE4 is through the sequestration of apoE proteins on the hepatic cell surface. The lower LDLR affinity of apoE2 increases plasma apoE levels (Blanchard et al, 2018). The elevated plasma FIGURE 3 | APOE alleles and post-prandial plasma triglyceride levels (TG).…”