Type 2 Diabetes (T2D) -Dependent Neurodegeneration: Investigation of Serum Protein Glycation and Glycosylation Biomarkers for Early Detection

Type 2 Diabetes (T2D), an age related disease, is a growing epidemic with approximately 7% of the world’s population suffering from it and over 25% among those above the age of 50.

T2D is also linked to an increased susceptibility to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The toxicity excreted in T2D is due to the binding of monosaccharides to lysines and arginines in serum proteins, leading to change or loss of function, change or loss of structure, crosslinking to other proteins and activation of inflammatory pathways through advanced glycation end-product (AGE). Here we compare time-course serum samples for T2D patients who showed cognitive decline with patients who remained cognitively normal over time. We quantified site-specific AGEs, as well as N- and O-glycosylation, determining the difference in glycation and glycosylation patterns between the two groups. Our goal is to identify the earliest occurrence of cognitive impairment-related biomarkers and the time lapse between their occurrence and the emergence of frank clinical phenotypes.