An increased plasma level of apociii-rich electronegative high-density lipoprotein may contribute to cognitive impairment in alzheimer’s disease

Hua Chen Chan, Liang Yin Ke, Hsiao Ting Lu, Shih Feng Weng, Hsiu Chuan Chan, Shi Hui Law, I. Ling Lin, Chuan Fa Chang, Ye Hsu Lu, Chu Huang Chen, Chih Sheng Chu

Research output: Contribution to journalArticlepeer-review

Abstract

High-density lipoprotein (HDL) plays a vital role in lipid metabolism and anti-inflammatory activities; a dysfunctional HDL impairs cholesterol efflux pathways. To understand HDL’s role in patients with Alzheimer’s disease (AD), we analyzed the chemical properties and function. HDL from AD patients (AD-HDL) was separated into five subfractions, H1–H5, using fast-protein liquid chromatography equipped with an anion-exchange column. Subfraction H5, defined as the most electronegative HDL, was increased 5.5-fold in AD-HDL (23.48 ± 17.83%) in comparison with the control HDL (4.24 ± 3.22%). By liquid chromatography mass spectrometry (LC/MSE), AD-HDL showed that the level of apolipoprotein (apo)CIII was elevated but sphingosine-1-phosphate (S1P)-associated apoM and anti-oxidative paraoxonase 1 (PON1) were reduced. AD-HDL showed a lower cholesterol efflux capacity that was associated with the post-translational oxidation of apoAI. Exposure of murine macrophage cell line, RAW 264.7, to AD-HDL induced a vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts alongside a concomitant increase of tumor necrosis factor-α (TNF-α) detectable in the cultured medium. In conclusion, AD-HDL had a higher proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated increase in pro-inflammatory (apoCIII, TNF-α) components might favor Amyloid β assembly and neural inflammation. A compromised cholesterol efflux capacity of AD-HDL may also contribute to cognitive impairment.

Original languageEnglish
Article number542
Pages (from-to)1-16
Number of pages16
JournalBiomedicines
Volume8
Issue number12
DOIs
Publication statusPublished - 2020 Dec

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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