Duggan, Michael R.; Oh, Hamilton Se Hwee; Frank, Philipp; Gomez, Gabriela T.; Zweibaum, David A.; Cui, Yuhan; Chen, Jingsha; Surapaneni, Aditya L.; Blew, Cassandra O.; Dark, Heather E.; Joynes, Cassandra M.; Kandala, Sri; Bilgel, Murat S.; Farinas, Amelia; Erus, Guray; Tian, Qu; Candia, Julián; Pucha, Krishna Ananthu; Landman, Bennett Allan; Dumitrescu, Logan C.; Hohman, Timothy J.; Lewis, Alexandria; Moghekar, Abhay R.; Siavoshi, Fatemeh; Ali, Muhammad; Liu, Menghan; Xu, Ying; Western, Daniel; Kaneko, Naoto; Kato, Shintaro; Furuichi, Makio; Shibayama, Masaki; Katsuno, Masahisa; Nishita, Yukiko; Otsuka, Rei; Gottesman, Rebecca F.; Dammer, Eric B.; Seyfried, Nicholas T.; Levey, Aĺlan I.; B Johnson, Erik C.; Mormino, Elizabeth C.; Wagner, Anthony D.; Poston, Kathleen Lombard; Kapogiannis, Dimitrios; Grams, Morgan E.; Bhargava, Pavan; Waga, Iwao; Davatzikos, Christos A.; Resnick, Susan M.; Ferrucci, Luigi G.; Bennett, David Alan; Cruchaga, Carlos C.; Wyss-Coray, Tony; Kivimaki, Mika Shipley; Coresh, Josef; & Walker, Keenan A. (2026). OMG! A proteomic determinant of neurodegenerative resiliency. Molecular Neurodegeneration, 21(1), 9. https://doi.org/10.1186/s13024-025-00921-1
Studying proteins in body fluids, known as biofluid proteomics, can help scientists better understand the biological changes that occur in Alzheimer’s disease and related dementias, collectively called ADRDs. One protein of interest is oligodendrocyte myelin glycoprotein, or OMG. OMG is found mainly in the brain and is involved in myelination, the process that forms the protective coating around nerve fibers. However, its exact role in disease mechanisms, its usefulness as a biomarker, and its potential as a treatment target in ADRDs are not fully understood.
In this study, researchers first observed that lower levels of OMG in the blood were linked to higher levels of cortical amyloid deposition, a buildup of amyloid plaques in the brain that is a hallmark of Alzheimer’s disease, in two community-based groups. They then examined OMG more extensively using high-throughput proteomics data from sixteen independent cohorts across North America, Europe, and Asia. These included both cross-sectional studies, which look at people at a single time point, and longitudinal studies, which follow people over many years. The analysis included multiple biofluids such as blood plasma and cerebrospinal fluid (CSF), as well as brain tissue samples, and used different proteomic technologies.
The results showed that lower plasma OMG levels were associated with amyloid buildup, poorer brain structure, dementia, and multiple sclerosis. Lower OMG was also found in people who later developed dementia over follow-up periods ranging from 7 to 20 years. Proteomic patterns in CSF and brain tissue suggested that OMG is linked to neuroprotective processes, especially those that maintain axonal structural integrity, which is essential for healthy communication between nerve cells. In addition, two-sample Mendelian randomization, a genetic method used to assess potential causal relationships, indicated that higher OMG levels may protect against several neurodegenerative diseases.
Overall, these findings suggest that OMG plays an important role in neurodegenerative resilience in older adults and that its level in the blood may serve as a reliable indicator of this protective effect.
Fig. 1
Study overview. The current study leveraged proteomics from the Baltimore Longitudinal study of Aging (BLSA), the Atherosclerosis risk in Communities study (ARIC), the Emory AD Research Center (Emory-ADRC; EADRC), a Stanford University cohort (i.e., participants enrolled in the Iqbal Farrukh and Asad Jamal Stanford ad Research Center, the Stanford Aging and Memory study, the Stanford Biomarkers in PD study, and the Stanford Center for Memory Disorders cohort study), the Religious Orders study/Rush Memory and Aging Project (ROSMAP), the Knight ad Research Center (Knight-ADRC; KADRC), a Hong Kong AD cohort (HKADC), the Women’s Health Initiative (WHI), the UK Biobank (UKB), the AD Neuroimaging Initiative (ADNI), the National Institute for Longevity Sciences-Longitudinal study of Aging (NILS-LSA), the Whitehall II cohort, the Cardiovascular Health study (CHS), the Generation Scotland study (GenS), the Johns Hopkins multiple sclerosis Center (JHMSC), and the Johns Hopkins Neurology cohort (JHN). *previously computed results were obtained for HKADC, WHI, CHS, and GenS. JHMSC analyses examined prevalent multiple sclerosis, not dementia