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<p>Blood-based biomarkers are emerging as scalable tools for the diagnosis and monitoring of neurodegenerative diseases, but markers enabling differential diagnosis across major dementias remain limited. Here we show that large-scale plasma proteomics identifies disease-associated signatures across Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia. We analyzed 1,318 plasma samples from well-characterized international cohorts and identified more than 200 dysregulated proteins across disease groups. Glial fibrillary acidic protein showed the strongest increase along the Alzheimer’s disease continuum, whereas integrin alpha-V and integrin alpha-M were consistently reduced in Lewy body disorders, including autopsy-confirmed cases. Elevated neurofilament light chain and lower glial fibrillary acidic protein were associated with frontotemporal dementia. We translated these findings into a 21-protein quantitative multiplex panel and validated it in an independent multicenter cohort (<i>n</i> = 805). These findings support plasma proteomics as an approach for biomarker-based differential diagnosis and disease staging across major neurodegenerative dementias.</p>

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Plasma proteome profiling identified biomarkers for the differential diagnosis and molecular staging of neurodegenerative dementias

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Giovanni Bellomo,
  • Lisa Vermunt,
  • Sjors in ‘t Veld,
  • James D. Doecke,
  • Yanaika S. Hok-A-Hin,
  • Kateřina Veverová,
  • Isabel M. Houtkamp,
  • Daniel Alcolea,
  • Steffen Halbgebauer,
  • Carlos Quesada,
  • Niklas Mattsson,
  • Minerva Martinez-Castillo,
  • María José López-Martínez,
  • Alberto Rábano,
  • Lynn Boonkamp,
  • Christopher Fowler,
  • Juan Fortea,
  • Lorenzo Gaetani,
  • Andrea Toja,
  • Yolande Pijnenburg,
  • Afina Lemstra,
  • Wiesje M. van der Flier,
  • Pascual Sánchez-Juan,
  • Jakub Hort,
  • Markus Otto,
  • Sarah Anderl-Staub,
  • Anne Sieben,
  • Bart de Viel,
  • Sebastiaan Engelborghs,
  • Oskar Hansson,
  • Colin Masters,
  • Alberto Lleó,
  • Lucilla Parnetti,
  • Charlotte E. Teunissen,
  • Marta del Campo

摘要

Blood-based biomarkers are emerging as scalable tools for the diagnosis and monitoring of neurodegenerative diseases, but markers enabling differential diagnosis across major dementias remain limited. Here we show that large-scale plasma proteomics identifies disease-associated signatures across Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia. We analyzed 1,318 plasma samples from well-characterized international cohorts and identified more than 200 dysregulated proteins across disease groups. Glial fibrillary acidic protein showed the strongest increase along the Alzheimer’s disease continuum, whereas integrin alpha-V and integrin alpha-M were consistently reduced in Lewy body disorders, including autopsy-confirmed cases. Elevated neurofilament light chain and lower glial fibrillary acidic protein were associated with frontotemporal dementia. We translated these findings into a 21-protein quantitative multiplex panel and validated it in an independent multicenter cohort (n = 805). These findings support plasma proteomics as an approach for biomarker-based differential diagnosis and disease staging across major neurodegenerative dementias.