Dissecting Alzheimer’s disease molecular substrates by proteomics and discovery of novel post-translational modifications (PTMs)

Protein post-translational modifications (PTMs) serve as diagnostic markers in Alzheimer’s disease. We aimed to discover new PTMs in the context of this disease from MS/MS-based proteomic datasets. Publicly available label-free proteomics data were searched for select PTMs using SEQUEST-HT. Only high-confidence PTMs were analyzed further using bioinformatics analysis. We identified 4,961 unique modified peptides corresponding to 1,856 proteins from datasets pertaining to Alzheimer’s disease. Of these, 52 proteins were known to be involved in Alzheimer’s pathway. Also, 3,164 PTMs are reported to be novel in the context of this disease. Further, protein quantification reveals expression of 13 high-abundant secretary proteins across multiple studies which can be exploited as biomarkers. Identification of novel PTMs from the publicly available proteomic data may provide novel molecular insights in the progression and management of Alzheimer’s disease. Novel high abundant secretory proteins identified can be candidate CSF biomarkers in Alzheimer’s disease.