Correlations between the NMR Lipoprotein Profile, APOE Genotype, and Cholesterol Efflux Capacity of Fasting Plasma from Cognitively Healthy Elderly Adults

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2186
• Main Authors: de Rojas, Itziar, Del Barrio, Laura, Hernández, Isabel, Montrreal, Laura, García-González, Pablo, Marquié, Marta, Valero, Sergi, Cano, Amanda, Orellana, Adelina, Boada, Mercè, Mañes, Santos, Ruiz, Agustín
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-01-2023; MDPI
• Subjects: ABC transporters; Adult; Aged; Alzheimer's disease; Animal models; Animals; APOE; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - genetics; Blood plasma; Cholesterol; cholesterol efflux capacity (CEC); Cholesterol, HDL; Correlation; Efflux; elderly adults; Fasting; Genomes; Genotype; Genotype & phenotype; Genotypes; High density lipoprotein; Humans; Ketones; Lipids; Lipoproteins; Macrophages; Magnetic Resonance Spectroscopy; Male; Metabolites; Metabolomics; Mice; NMR; Nuclear magnetic resonance; Older people; Parkinson's disease; Plasma; Variables; cholesterol efflux capacity (CEC); APOE; Alzheimer’s disease; elderly adults
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032186

Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of the
locus in mouse models supports the idea that it is involved in determining the CEC. With that in mind, we examine the impact of the plasma metabolome profile and the
genotype on the CEC in cognitively healthy elderly subjects. The study subjects were 144 unrelated healthy individuals. The plasma CEC was determined by exposing cultured mouse macrophages treated with BODIPY-cholesterol to human plasma. The metabolome profile was determined using NMR techniques. Multiple regression was performed to identify the most important predictors of CEC, as well as the NMR features most strongly associated with the
genotype. Plasma 3-hydroxybutyrate was the variable most strongly correlated with the CEC (r = 0.365;
= 7.3 × 10
). Male sex was associated with a stronger CEC (r = -0.326,
= 6.8 × 10
). Most of the NMR particles associated with the CEC did not correlate with the
genotype. The NMR metabolomics results confirmed the
genotype to have a huge effect on the concentration of plasma lipoprotein particles as well as those of other molecules including omega-3 fatty acids. In conclusion, the CEC of human plasma was associated with ketone body concentration, sex, and (to a lesser extent) the other features of the plasma lipoprotein profile. The
genotype exerted only a weak effect on the CEC via the modulation of the lipoprotein profile. The
locus was associated with omega-3 fatty acid levels independent of the plasma cholesterol level.