Lipoprotein-Based Nanoparticles Rescue the Memory Loss of Mice with Alzheimer’s Disease by Accelerating the Clearance of Amyloid-Beta

Abstract

Amyloid-beta (Aβ) accumulation in the brain is believed to play a central role in Alzheimer's disease (AD) pathogenesis, and the common late-onset form of AD is characterized by an overall impairment in Aβ clearance. Therefore, development of nanomedicine that can facilitate Aβ clearance represents a promising strategy for AD intervention. However, previous work of this kind was concentrated at the molecular level, and the disease-modifying effectiveness of such nanomedicine has not been investigated in clinically relevant biological systems. Here, we hypothesized that a biologically inspired nanostructure, apolipoprotein E3-reconstituted high density lipoprotein (ApoE3-rHDL), which presents high binding affinity to Aβ, might serve as a novel nanomedicine for disease modification in AD by accelerating Aβ clearance. Surface plasmon resonance, transmission electron microscopy, and co-immunoprecipitation analysis showed that ApoE3-rHDL demonstrated high binding affinity to both Aβ monomer and oligomer. It also accelerated the microglial, astroglial, and liver cell degradation of Aβ by facilitating the lysosomal transport. One hour after intravenous administration, about 0.4% ID/g of ApoE3-rHDL gained access to the brain. Four-week daily treatment with ApoE3-rHDL decreased Aβ deposition, attenuated microgliosis, ameliorated neurologic changes, and rescued memory deficits in an AD animal model. The findings here provided the direct evidence of a biomimetic nanostructure crossing the blood-brain barrier, capturing Aβ and facilitating its degradation by glial cells, indicating that ApoE3-rHDL might serve as a novel nanomedicine for disease modification in AD by accelerating Aβ clearance, which also justified the concept that nanostructures with Aβ-binding affinity might provide a novel nanoplatform for AD therapy.

Targeted Therapies for Alzheimer's Disease: An Overview

“…It also accelerated the microglial, astroglial, and liver cell degradation of Aβ by facilitating the lysosomal transport. The findings here provided the direct evidence of a biomimetic nanostructure crossing the blood-brain barrier, capturing Aβ and facilitating its degradation by glial cells, indicating that ApoE3-rHDL might serve as a novel nanomedicine for disease modification in AD by accelerating Aβ clearance, which also justified the concept that nanostructures with Aβ-binding affinity might provide a novel nanoplatform for AD therapy [7].some researchers made an attempt to targetthe anti-Alzheimer's drug rivastigmine in the brain by using poly (n-butylcyanoacrylate) nanoparticles. The drug was administered as a free drug, bound to nanoparticles and alsobound to nanoparticles coated with polysorbate 80.…”

A Plant Phytosulfokine Peptide Initiates Auxin-Dependent Immunity through Cytosolic Ca2+ Signaling in Tomato

“…Activation, deactivation, and preparation of the coupled flow cell as well as the ligand binding assay were performed essentially as described previously (Song et al, 2014). Briefly, the recombinant PSKR1-and PSKR2-encoding proteins were immobilized in parallel-flow channels of the CM5 sensor chip using an amine coupling kit (GE Healthcare).…”

“…Briefly, the recombinant PSKR1-and PSKR2-encoding proteins were immobilized in parallel-flow channels of the CM5 sensor chip using an amine coupling kit (GE Healthcare). To test PSK binding to potential receptors, serial concentrations of PSK or dPSK (diluted in 0.01 M PBS, pH 7.4) were injected into the flow system (Song et al, 2014). Experiments were conducted with PBS (pH 7.4) as the running buffer, and the analyte was injected at a flow rate of 30 mL/min.…”

Green design “bioinspired disassembly-reassembly strategy” applied for improved tumor-targeted anticancer drug delivery

“…They form core-shell spherical or discoidal nanoparticles of 7-600 nm in vivo to transport waterinsoluble lipids for peripheral usage [16,17]. Structurally, the amphiphilic nature of the lipids is capable of stabilizing the lipophilic cores, while the anchored apolipoproteins maintain the hydrodynamic size of the self-assembled natural nanoparticles [18,19]. Furthermore, lipoproteins possess specific affinity to their endogenous receptors in vivo.…”