An atlas of the aging glycoproteome reveals how glycosylation modulates autoantibody binding in the brain

Aging in mouse brain is linked to increased short paucimannose N-glycans, including HEXB-driven remodeling that raises paucimannosylation of MOG at N60 in white matter.

• Why it matters: Glycan composition shifts with age, but its brain-specific patterns and how they affect autoantibody recognition—especially for MOG in central nervous system autoimmunity—remain unclear.
• What they did: The study mapped N-glycopeptides across five mouse tissues and nine ages, identifying 80,618 unique N-glycopeptides at 9,211 glycosites, then tested MOG N60 glycan effects on binding and used EAE to model shared changes.
• The result: MOG-reactive autoantibodies were found in aged individuals and in patients with MOG antibody-associated disease, and the MOG N60 glycan is linked to autoantibody binding, with EAE recapitulating a subset of age-associated glycosite changes.

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