OMG as a Marker of Resiliency to Neurodegenerative Processes
Researchers here provide evidence for circulating oligodendrocyte myelin glycoprotein (OMG, and the expected joking reference is made in the paper's title) to correlate with the state of neurodegeneration in the aging brain. Interestingly, further investigations indicated that OMG is actively protective, not just a marker of protection, and thus one can envisage efforts to increase its expression in the brain as a basis for future therapies to make the brain more resilient to the damage of aging. That process of development is ever a long one, of course, and it is hard to predict timelines for moving from identification of a target to a viable approach to therapy.
After identifying oligodendrocyte myelin glycoprotein (OMG) as a central nervous system (CNS)-specific protein whose levels in peripheral circulation were inversely associated with cortical amyloid-β deposition in two community-based cohorts, the current study leveraged high-throughput plasma proteomic data from over a dozen independent cohorts to characterize OMG's role in Alzheimer's disease and other age-related dementias. We found lower plasma OMG levels among individuals with dementia, compromised brain structure (measured with MRI), and multiple sclerosis (MS). Additionally, individuals with lower plasma OMG were at elevated risk for future dementia and faster cognitive decline.
Using its multi-cohort, cerebrospinal fluid (CSF) proteomic signature, we demonstrated that higher OMG abundance is reflective of broader neuronal and oligodendroglial mechanisms that primarily promote the maintenance of axonal structural stability, along with cell adhesion, synaptic functioning, and proteostasis. Having identified similar structural- and axonal-integrity pathways in OMG's conserved brain tissue proteomic signature, we used genetic inference techniques to show that the cis regulation of OMG abundance across biofluids and brain tissue is causally implicated as protective against multiple neurodegenerative diseases.