# OMG! A proteomic determinant of neurodegenerative resiliency

## TL;DR

This study identifies a brain protein called OMG that may protect against neurodegenerative diseases like Alzheimer's, as lower levels in the blood are linked to disease progression.

## Contribution

The study reveals OMG as a novel biomarker and potential therapeutic target for neurodegenerative resiliency.

## Key findings

- Lower plasma OMG levels are associated with cortical amyloid deposition, brain structure compromise, and dementia.
- OMG's signatures in cerebrospinal fluid and brain proteomics suggest roles in axonal integrity and neuroprotection.
- Mendelian randomization supports a causal protective role of OMG against multiple neurodegenerative diseases.

## Abstract

Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer’s disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation.

After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG’s role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, and proteomic platforms. Statistical analyses were conducted separately in each cohort.

We detected lower plasma OMG in individuals with cortical amyloid deposition, compromised brain structure, dementia, and multiple sclerosis, as well as in individuals who developed dementia over 7- to 20-year follow-up periods. OMG’s CSF and brain proteomic signatures reflected broader neuroprotective mechanisms, especially axonal structural integrity, and two-sample Mendelian randomization causally implicated OMG as protective against multiple neurodegenerative diseases.

Our findings implicate OMG as a mechanistic determinant of neurodegenerative resiliency among older adults, which is reliably captured by its abundance in peripheral circulation

The online version contains supplementary material available at 10.1186/s13024-025-00921-1.