Quantitative proteome analysis of S-nitrosylation on synaptosomal proteins in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is an irreversible, progressive and most common type of dementia in the aging population. AD pathophysiology starts slowly and deteriorates over time before the clinical diagnosis of dementia can be made. Neuropathologic features of AD are the presence of amyloid deposits, neurofibrillary tangles, synapse loss and neurodegeneration. Increasing evidence proposes neuroinflammation as one of the essential components of AD pathogenesis. Numerous studies have shown the involvement of protein s-nitrosylation in the development of AD pathology. The current study targeted s-nitrosylation in synaptosomal proteins, which have been isolated from mouse and human brain tissues using an isobaric mass tag (iodoTMT) method and nanocapillary high performance liquid chromatography tandem mass spectrometry (nanoHPLC MS/MS). Mice samples were collected and analyzed according to their age (3-months and 12-month-old mice) and genotype (APP/PS1 and NOS2 knockout on 12-month-old mice) effects. Data obtained from murine AD models were then compared to brain samples from Alzheimer's disease, mild cognitive impairment (MCI) and healthy elderly subjects. The results represent a candidate list of s-nitrosylated synaptic proteins isolated from mouse and human samples, which could be further evaluated as early biomarkers in AD. In addition, the iodoTMT method has been confirmed for the analyzation of S-nitrosylation instable protein modifications, particularly in studies with finite sample materials.