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Depletion of amyloid‐β peptides from solution by sequestration within fibril‐seeded hydrogels
Author(s) -
Yau WaiMing,
Tycko Robert
Publication year - 2018
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3387
Subject(s) - self healing hydrogels , amyloid fibril , fibril , chemistry , biophysics , amyloid (mycology) , peptide , chemical engineering , biochemistry , amyloid β , pathology , biology , polymer chemistry , medicine , inorganic chemistry , disease , engineering
Abstract Aggregation of amyloid‐β (Aβ) peptides in brain tissue leads to neurodegeneration in Alzheimer's disease (AD). Regardless of the kinetics or detailed mechanisms of Aβ aggregation, aggregation can only occur if Aβ concentrations exceed their local equilibrium solubility values. We propose that excess Aβ peptides can be removed from supersaturated solutions, including solutions in biological fluids, by the addition of hydrogels that are seeded with Aβ fibril fragments. Fibril growth within the hydrogels then sequesters excess peptides until equilibrium concentrations are reached. Experiments with 40‐ and 42‐residue Aβ peptides (Aβ40 and Aβ42) 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. Aβ 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.