Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis

Sci Rep. 2017 Nov 7;7(1):14637. doi: 10.1038/s41598-017-15215-w.

Abstract

Cerebral β-amyloidosis is a major feature of Alzheimer's disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Aβ, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ). Hence, rHDL particles were prepared using the cholate dialysis method and characterized by N-PAGE, dynamic light scattering, circular dichroism and electron transmission microscopy. The preparation of rHDL particles showed two-sized populations with discoidal shape. Functionally, rHDL-rApoJ maintained the ability to prevent the Aβ fibrillization and mediated a higher cholesterol efflux from cultured macrophages. Fluorescently-labelled rHDL-rApoJ nanoparticles were intravenously administrated in mice and their distribution over time was determined using an IVIS Xenogen® imager. It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Aβ load. In conclusion, we have standardized a reproducible protocol to produce rHDL-rApoJ nanoparticles, which may be potentially considered as a therapeutic option for β-amyloid-related pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Amyloidosis / metabolism
  • Amyloidosis / pathology
  • Amyloidosis / therapy*
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Clusterin / administration & dosage*
  • Clusterin / chemistry
  • Disease Models, Animal
  • Humans
  • Lipoproteins, HDL / administration & dosage*
  • Lipoproteins, HDL / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nanocomposites / administration & dosage*
  • Nanocomposites / chemistry
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / prevention & control*

Substances

  • CLU protein, human
  • Clusterin
  • Lipoproteins, HDL