Abstract
The deposition of amyloid-β (Aβ) plaques in the brain is a significant pathological signature of Alzheimer’s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop Aβ aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), which is derived from the receptor binding sequence of apolipoprotein E, is effectively able to inhibit Aβ aggregation and to promote fibril disaggregation. Taking advantage of Atomic Force Microscopy (AFM) imaging and fluorescence techniques, we investigate if the clustering of mApoE on gold nanoparticles (AuNP) surface may affect its performance in controlling Aβ aggregation/disaggregation processes. The results showed that the ability of free mApoE to destroy preformed Aβ fibrils or to hinder the Aβ aggregation process is preserved after its clustering on AuNP. This allows the possibility to design multifunctional drug delivery systems with clustering of anti-amyloidogenic molecules on any NP surface without affecting their performance in controlling Aβ aggregation processes.
Highlights
The aggregative behavior of amyloid-β (Aβ) peptide, which is considered by many as responsible for the development of Alzheimer’s disease (AD), has been extensively analyzed for many years
We investigate if the anti-aggregative properties of mApoE against Aβ are preserved after its deposition on the AuNP surface
Our findings suggest that both free peptide and mApoE-AuNP hinder Aβ aggregation and disassemble preformed Aβ fibrils, as already described using liposomes functionalized with mApoE [38,39]
Summary
The aggregative behavior of amyloid-β (Aβ) peptide, which is considered by many as responsible for the development of Alzheimer’s disease (AD), has been extensively analyzed for many years. To study the aggregation patterns of amyloid proteins (i.e., formation of water-soluble aggregates), as well as to monitor the disaggregation process of fibrils into smaller water-soluble aggregates, several biophysical techniques, capable of providing information about the various steps in Aβ aggregation, have been extensively applied. Scattering is blind to aggregates smaller than about 10 nm. This implies that the earliest events in the aggregation process are perceived as a “lag time” in such measurements. Due to the low scattering signal, scattering measurements are hardly applicable on samples diluted below several micromoles/liter, while, in the case at hand, Aβ concentrations in the cerebrospinal fluid of AD patients are
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