Biomolecular Corona Dictates Aβ Fibrillation Process

Area of Science:

• Biomaterials Science
• Neuroscience
• Nanotechnology

Background:

• Amyloid beta (Aβ) aggregation into toxic oligomers and fibrils is central to Alzheimer's disease pathology.
• Nanoparticles (NPs) are investigated for their potential to modulate Aβ fibrillation.
• The influence of the biomolecular corona, formed on NPs in biological fluids, on Aβ fibrillogenesis is often overlooked.

Purpose of the Study:

• To investigate the impact of biomolecular coronas from human cerebrospinal fluid (CSF) and plasma on amyloid beta (Aβ) fibrillation.
• To understand how corona composition affects the antifibrillation efficacy of therapeutic nanoparticles.

Main Methods:

• Studied the fibrillation of Aβ_1-42 and Aβ_25-35 peptides in the presence of pristine and biomolecular corona-coated gold nanoparticles (NPs).
• Utilized biomolecular coronas derived from human CSF and plasma.
• Compared the fibrillation kinetics of Aβ peptides with different NP surface conditions (pristine, CSF-corona, plasma-corona).

Main Results:

• The type of biomolecular corona dictates whether NPs inhibit or accelerate Aβ fibrillation.
• Plasma corona-coated gold NPs exhibited less inhibition on Aβ_1-42 fibrillation compared to CSF-corona and pristine NPs.
• Pristine NPs accelerated Aβ_25-35 fibrillation, while corona-coated NPs inhibited it, with CSF corona showing less inhibition than plasma corona.

Conclusions:

• The biomolecular corona on NPs plays a crucial role in modulating Aβ fibrillation, influencing the therapeutic potential of NPs.
• Understanding corona-NP-Aβ interactions is essential for designing effective nanoparticle-based therapies for Alzheimer's disease.
• Different biological fluids (plasma vs. CSF) yield distinct coronas that differentially affect Aβ aggregation pathways.