Analytical methods to explore Amyloid-β-Peptide variants beyond Aβ1-40 and Aβ1-42

Aβ-peptides are believed to play a key role in the onset and progression of Alzheimerʼs disease and may thus represent targets for novel, disease modifying, causal therapies. Several Aβ variants differing in their amino- and carboxyl-termini exist, and some of these may be of particular pathophysiological relevance. Furthermore, specific Aβ variants can serve as surrogate biomarkers. The discrimination and unequivocal identification of different Aβ-species, some of which occurring in minute amounts in biological samples, is challenging. To this end, we employ different technologies, such as urea-SDS-polyacrylamide gel-electrophoresis, capillary isoelectric focusing followed by immunological detection, immunoprecipitation followed by matrix-assisted laser desorption mass spectrometry and two dimensional gel electrophoresis followed by Western-immunoblot detection.

This study was supported by FP7 EU grant NADINE (Grant Agreement Number 246513); grant PURE (Protein Research Unit Ruhr within Europe) from the State Government North Rhine-Westphalia; BioPharma-NeuroAllianz grant (161A120B/031A120B)