Depletion of amyloid-? peptides from solution by sequestration within fibril-seeded hydrogels.

ABSTRACT: Aggregation of amyloid-? (A?) peptides in brain tissue leads to neurodegeneration in Alzheimer's disease (AD). Regardless of the kinetics or detailed mechanisms of A? aggregation, aggregation can only occur if A? concentrations exceed their local equilibrium solubility values. We propose that excess A? peptides can be removed from supersaturated solutions, including solutions in biological fluids, by the addition of hydrogels that are seeded with A? fibril fragments. Fibril growth within the hydrogels then sequesters excess peptides until equilibrium concentrations are reached. Experiments with 40- and 42-residue A? peptides (A?40 and A?42) in phosphate buffer at 24°C and in filtered fetal bovine serum at 37°C, using crosslinked polyacrylamide hydrogels, demonstrate the validity of this concept. A? sequestration in fibril-seeded hydrogels (or other porous media) may prove to be a useful technique in experiments with animal models of AD and may represent a possible approach to preventing or slowing the progression of AD in humans.

SUBMITTER: Yau WM 

PROVIDER: S-EPMC6032349 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature