Cognitive Decline in Older Adults with Type 2 Diabetes: Unraveling Site-Specific Glycoproteomic Alterations

ABSTRACT: Type 2 diabetes (T2D) is consistently associated with an elevated risk of cognitive decline and dementia. The underlying molecular mechanisms relating T2D to cognitive decline remain unclear, impeding the ability to detect the earliest stages of cognitive decline in older adults with T2D, consequently hindering advancement of preventive interventions. This study compared quantitative alterations in glycoproteoforms, represented by tryptic glycopeptiforms—specific glycan compositions on amino acid sites of proteins—in older T2D adults. We utilized label free, mass spectrometry-based glycoproteomics to analyze protein N-glycosylation and glycation patterns in serum samples, collected at two time points (T1 and T2), an average 52 months apart, from two initially cognitively healthy T2D groups. One group was comprised of individuals who experienced cognitive decline (“decliners”; N=8), and the other, of individuals who maintained normal cognition (“non-decliners”; N=14) over time. Comparison of these two groups revealed distinct patterns for glycosylation and glycation. Glycosylation primarily affected platelet function pathways. Glycation was also involved in immune system and platelet function along with various metabolic pathways. These findings suggest that aberrant glycoproteomic modifications may contribute to the development of cognitive impairment in T2D and may serve as potential early biomarkers. Further research is warranted to elucidate the functional implications of glycopeptiform modifications in T2D-related cognitive decline.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Dementia

SUBMITTER: Yishai Levin  

LAB HEAD: Michal Schnaider Beeri

PROVIDER: PXD050780 | Pride | 2025-02-16

REPOSITORIES: pride