OMG (oligodendrocyte myelin glycoprotein) is a brain-specific cell adhesion molecule that functions as a determinant of neurodegenerative resiliency 1. Mechanistically, OMG contributes to the interactive processes required for myelination in the central nervous system [UniProt annotation] and maintains axonal structural integrity 1. Lower circulating OMG levels are associated with cortical amyloid deposition, compromised brain structure, and dementia diagnosis 1. Prospectively, reduced plasma OMG predicts cognitive decline over 7-20 year follow-up periods, with two-sample Mendelian randomization analyses supporting OMG as causally protective against multiple neurodegenerative diseases including Alzheimer's disease and related dementias 1. Additionally, lower OMG levels are detected in multiple sclerosis, another neurodegenerative condition 1. Clinically, peripheral blood OMG abundance reliably captures neuroprotective mechanisms and represents a promising biomarker for neurodegenerative disease risk stratification in older adults 1. These findings position OMG as a mechanistically relevant protein bridging myelination biology with neurodegeneration, though therapeutic applications remain to be developed.