Introduction
Alzheimer’s disease(AD) is the most common socially significant neurodegenerative pathology worldwide. Since existing therapy methods are low-effective, development of reliable early diagnostics approaches is one of the global tasks. Increasing attention is being paid to AD-associated blood plasma proteome changes, including post-translational modifications (PTMs) studies. Mass spectrometry (MS) approaches seem to be the most promising tool due to high sensitivity, specificity, and multiplexing capacity.
Methods
Plasma samples were collected from three groups of patients – AD (16), mild cognitive impairment (MCI, 20) mentally healthy elders (14). Plasma was subjected to abundant protein depletion, denaturation, filtration, alkylation and trypsinolysis (16 hours, 37C). Samples were analyzed by LC-ESI-MS/MS using nano-LC Agilent 1100 system coupled to 7T LTQFT Ultra tandem high-resolution mass-spectrometer.
Results and Conclusions
Significant changes in plasma levels of 22 proteins were observed, including 14 whose dysregulation was previously shown to be associated with AD/MCI in studies on CSF and postmortem brains. Obtaining consistent results on different cohorts using different methods is an extremely important stage for validation of pathology markers and one of the central tasks for determination of biomarkers specific for AD and MCI. Analysis PTMs distribution showed significant changes correlating with pathologies in modification levels even for those proteins whose expression levels remain unchanged. Since early AD diagnostics methods remain a hot issue, obtained results may be important for creation of new MS-based diagnostics methods.