Top-down proteomics of human saliva in Alzheimer disease

Alzheimer disease (AD) is the most prevalent neurodegenerative disease and form of dementia in the elderly. It is characterized by the accumulation in the brain of misfolded proteins, inflammation and oxidative damage leading to region-specific loss of synaptic contacts and neuronal cell death. In the present study, we aimed to characterize the salivary protein profile of a sample (sample group or cohort) of AD patients in comparison with healthy controls (HC) by a top-down proteomic approach, to evidence possible quali-/quantitative variations associated to the disease. This approach is based on high performance liquid chromatography separation coupled to electrospray-ion trap mass spectrometry (HPLC-ESI-IT-MS) analysis of the acidic soluble proteome of human saliva, which was standardized in our previous studies for detecting and quantifying of hundreds salivary peptides/proteins. By this, it is possible to obtain a profiling of the naturally occurring salivary proteome, including isoforms and post-translational modifications (PTMs), to compare an unlimited number of samples and to quantify proteins by a label-free method.