Understanding Alzheimer's disease by global quantification of protein phosphorylation and sialylated N-linked glycosylation profiles: A chance for new biomarkers in neuroproteomics?

Phosphorylation and glycosylation are important protein modifications in the mammalian brain acting as drivers of neural development, neurotransmission signalling and neurite elongation as well as synaptic morphology. Despite their important functional roles in the brain, only a few studies have elucidated them in neurodegenerative diseases such as Alzheimer's disease. Here, we comprehensively review Alzheimer's pathology in relation to protein phosphorylation and glycosylation on synaptic plasticity from neuroproteomics data. Moreover, we highlight several mass spectrometry-based sample processing technologies including an in-house developed TiO2 -SIMAC-TiO2 -based enrichment protocol to isolate and enrich phosphorylated and glycosylated peptides enabling to elucidate hopefully new early disease biomarkers.