Reduced cholesterol efflux capacity of HDL particles from Alzheimer's disease patients is not related to differences in lipoprotein profiles. (December 2021)

• Record Type: Journal Article
• Authors: Hong, Brian V.; Agus, Joanne; Sacchi, Romina; Rhodes, Christopher H.; Maezawa, Izumi; Jin, Lee‐Way; Harvey, Danielle J.; Lebrilla, Carlito B.; Zivkovic, Angela M.
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.052702
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: High density lipoproteins (HDL) are primarily known for their critical role in regulating cellular cholesterol concentrations via their capacity to induce cholesterol efflux from cells. HDL are also carriers of apolipoprotein E (ApoE), which is the strongest known genetic risk factor for AD. The main objective of this study was to determine the cholesterol efflux capacity of HDL particles isolated from plasma of APOE genotyped AD patients vs. age‐matched cognitively normal controls, and to characterize plasma lipoprotein profiles using size exclusion chromatography. Method: HDL particles were isolated from plasma samples of 10 AD patients (n=5 APOE3/E3, n=5 APOE3/E4) and 5 cognitively normal controls (n=5 APOE3/E3) using sequential ultracentrifugation followed by size exclusion chromatography. FPLC chromatograms were processed to adjust baseline values and calculate area under the curve (AUC) for LDL, HDL, and albumin using UNICORN 5.0 software. AUCs were used to estimate the relative distributions of fractions, including small and large HDL, and peak elution volume was used to estimate particle size most abundant in each fraction. Cholesterol efflux capacity of the isolated HDL particles was determined in PBMC‐derived macrophages using a fluorescently labeled cholesterol assay kit. Result: HDL from AD patients had dramatically reduced cholesterol efflux capacity compared with controls (36.0% ± 1.2% vs. 26.0% ± 1.2%, P<0.0001), with no difference between AD patients by APOE genotype (APOE3/E3, 25.9% ± 0.9%; APOE3/E4, 26.5% ±1.3%; P=0.21). There were no significant differences in the relative distributions or average particle sizes of HDL, LDL, albumin, or large and small HDL between patients and controls. These results suggest neither the amount nor size distribution of HDL particles is adequate to detect the main difference driving the diminished cholesterol efflux capacity of HDL particles from AD patients. Conclusion: The results of this study support previous findings of decreased cholesterol efflux capacity of HDL in AD patients, and underscore the necessity for additional analyses to characterize the compositional differences driving this diminished functional capacity and to further understand HDL's role in AD pathology.