Alzheimer's β‐Amyloid Protein Is Covalently Modified when Dissolved in Formic Acid

Publisher Website
Google Scholar
Abstract
β‐Amyloid protein is a major protein component of neuritic plaques in the brain of Alzheimer's disease patients. A major advance in understanding the molecular biology of Alzheimer's disease came with the purification and sequencing of this protein. Because β‐amyloid protein is very insoluble, extreme conditions such as 88% formic acid were commonly used to dissolve its fibrils. We now report that 88% formic acid covalently modifies β‐amyloid protein fragments, probably by the formation of a formate ester to a serine in the protein. The t1/2 of the formylation is ∼3.5 h, and the t1/2 for hydrolysis of the formylated peptide is much longer, being 9.9 h in water and 66 h in HPLC eluant. This suggests that if formic acid is used in the purification of β‐amyloid protein or peptide fragments of this protein, it is likely that some formylated peptide will be present in subsequent studies. Although unrecognized modification of a protein is inherently undesirable, it is uncertain what effects this formylation will have on ensuing studies. Certainly, investigations into the immunologic, physical, and physiologic properties of β‐amyloid protein could be influenced.