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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>Our findings implicate OMG as a mechanistic determinant of neurodegenerative resiliency among older adults, which is reliably captured by its abundance in peripheral circulation</p>

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OMG! A proteomic determinant of neurodegenerative resiliency

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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  • Michael R. Duggan,
  • Hamilton Se-Hwee Oh,
  • Philipp Frank,
  • Gabriela T. Gomez,
  • David Zweibaum,
  • Yuhan Cui,
  • Jingsha Chen,
  • Aditya Surapaneni,
  • Cassandra O. Blew,
  • Heather E. Dark,
  • Cassandra M. Joynes,
  • Sridhar Kandala,
  • Murat Bilgel,
  • Amelia Farinas,
  • Guray Erus,
  • Qu Tian,
  • Julián Candia,
  • Krishna A. Pucha,
  • Bennett A. Landman,
  • Logan Dumitrescu,
  • Timothy J. Hohman,
  • Alexandria Lewis,
  • Abhay Moghekar,
  • Fatemeh Siavoshi,
  • Muhammad Ali,
  • Menghan Liu,
  • Ying Xu,
  • Daniel Western,
  • Naoto Kaneko,
  • Shintaro Kato,
  • Makio Furuichi,
  • Masaki Shibayama,
  • Masahisa Katsuno,
  • Yukiko Nishita,
  • Rei Otsuka,
  • Rebecca F. Gottesman,
  • Eric B. Dammer,
  • Nicholas T. Seyfried,
  • Allan I. Levey,
  • Erik C. B. Johnson,
  • Elizabeth Mormino,
  • Anthony D. Wagner,
  • Kathleen L. Poston,
  • Dimitrios Kapogiannis,
  • Morgan E. Grams,
  • Pavan Bhargava,
  • Iwao Waga,
  • Christos Davatzikos,
  • Susan M. Resnick,
  • Luigi Ferrucci,
  • David A. Bennett,
  • Carlos Cruchaga,
  • Tony Wyss-Coray,
  • Mika Kivimäki,
  • Josef Coresh,
  • Keenan A. Walker

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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