Abstract
Alzheimer's disease (AD) is nowadays the prominent cause of senile dementia. This pathology is characterized by aggregation of neurofibrillary tangles in cells and by the accumulation of amyloid plaques in the brain. Noteworthy, a phosphorylated protein (tau protein) and a peptide presenting two overlapping sequences of 40 or 42 residues named β-amyloid peptides 1-40 (AB 1-40) and 1-42 (AB 1-42), respectively, were related to such deleterious phenomena. Singularly, the neurotoxicity was primarily attributed to the amyloid peptide AB 1-42 form due to its capacity to fold into beta-sheets rendering it insoluble thus causing subsequent aggregation and accumulation in vivo. Regarding AD diagnosis relying on mass spectrometry, AB 1-42 and/or AB 1-40 were considered as relevant biomarkers being measured in cerebrospinal fluids (CSF), blood and urine. Under that context, we aimed at implementing an innovative method to evidence the depletion of circulating AB 1-42 amyloid peptide compared to the shorter AB 1-40 form indicating a pathologic state. We investigated Surface-Assisted Laser Desorption/Ionization Mass Spectrometry (SALDI-MS) in order to monitor the AB 1-40 / AB 1-42 ratio without any prior sample treatment or enrichment. Taking into account that β-amyloid peptide 1-42 can aggregate into beta-sheets depending on the experimental conditions, specific attention was devoted to sample integrity monitoring performed by circular dichroism experiments during SALDI-MS method development.