Synthesis aided structural determination of amyloid-β(1–15) glycopeptides, new biomarkers for Alzheimer's disease

Abstract

Unique tyrosine glycosylated amyloid-β(1–15) glycopeptides were synthesized with well-defined stereochemistry at the glycosidic linkages. Aided by these glycopeptides and tandem mass spectrometry analysis, the naturally existing amyloid-β glycopeptides, isolated from Alzheimer's disease patients, were determined to contain an α-linked N-acetyl galactosamine at the modified tyrosine 10 residue. Glycosylation can significantly impact the properties of amyloid-β as the glycopeptide has much lower affinity for Cu⁺ ions.