Nanoscale liquid chromatography and capillary electrophoresis coupled to electrospray mass spectrometry for the detection of amyloid-β peptide related to Alzheimer’s disease

Alzeihmer’s disease (AD) is a neurodegenerative disorder which is pathologically characterized by the progressive deposit in the brain of a specific form of amyloid, amyloid-β peptides (Aβ). As the latter circulate in the blood, their quantitation in plasma could allow a simple diagnosis of AD. Aβ are present in different variants, one of which contains 40 amino acid residues (Aβ1–40). In this work, nanoscale liquid chromatography (nano-LC) and capillary electrophoresis (CE) coupled to mass spectrometry (MS) were compared to determine the most appropriate technique for reaching the usual Aβ1–40 concentration in plasma or serum. Both a 50 μm I.D. CE capillary and a 75 μm I.D. nano-LC column were coupled to a single quadrupole mass spectrometer with a sheath-liquid electrospray (ESI) interface or a homemade nanospray interface, respectively. Capillary zone electrophoresis is a powerful separation technique, but its low sensitivity limits its use in the analysis of biological matrices. However, a column-switching set-up with a precolumn of 1 mm×300 μm I.D. packed with a C18 PepMap (3 μm) stationary phase and a nanocolumn of 15 cm×75 μm I.D. packed with the same stationary phase was found to be a successful technique which allowed detection of Aβ1–40 at the ng ml−1 level (a few hundred femtomoles injected) because of its higher sample loading capability.