Glycoproteome-Wide Discovery of Cortical Glycoproteins That May Provide Cognitive Resilience in Older Adults

ABSTRACT: Background and Objectives Molecular omics studies have identified proteins related to cognitive resilience but unrelated to Alzheimer disease and Alzheimer disease–related dementia (AD/ADRD) pathologies. Posttranslational modifications of proteins with glycans can modify protein function. In this study, we identified glycopeptiforms associated with cognitive resilience. Methods We studied brains from adults with annual cognitive testing with postmortem indices of 10 AD/ADRD pathologies and proteome-wide data from dorsal lateral prefrontal cortex (DLPFC). We quantified 11, 012 glycopeptiforms from DLPFC using liquid chromatography with tandem mass spectrometry. We used linear mixed-effects models to identify glycopeptiforms associated with cognitive decline correcting for multiple comparisons (p < 5 × 10−6). Then, we regressed out the effect of AD/ADRD pathologies to identify glycopeptiforms that may provide cognitive resilience.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Yishai Levin  

LAB HEAD: Yishai Levin

PROVIDER: PXD072371 | Pride | 2025-12-24

REPOSITORIES: Pride