A robust preparation method for the amyloidogenic and intrinsically disordered amyloid-α peptide

Recent findings suggest that amyloid-beta (A beta) may not be the only peptidic culprit for the cognitive decline observed in patients with Alzheimer's disease. A C-terminal fragment of A beta, amyloid-alpha (A alpha), also known as p3, has been shown to form amyloidogenic oligomers and fibrils more rapidly than A beta. However, the insolubility and aggregation propensity of this 24-26-residue peptide make it exceptionally difficult to produce, purify, and subsequently study. This paper reports a reproducible, multi-step method for the purification and pre-treatment of A alpha and related analogues, yielding 95%-99% pure peptides. We anticipate that the methods described herein will permit previously inaccessible biophysical and biological experiments that may be critical to understanding the role of this too long overlooked peptide in AD disease pathology.

Automated summary

Recent findings suggest that amyloid-beta (A beta) may not be the sole cause of cognitive decline in Alzheimer's disease. A C-terminal fragment of A beta, known as amyloid-alpha (A alpha), has been shown to form amyloidogenic oligomers and fibrils more rapidly. However, its insolubility and aggregation propensity present challenges in production and study. This paper presents a reproducible method for the purification and pre-treatment of A alpha and related analogues, enabling further research on the role of this overlooked peptide in Alzheimer's disease pathology.