Plasma proteome profiling identified biomarkers for the differential diagnosis and molecular staging of neurodegenerative dementias
Nature Aging, 2026
Bellomo G., Vermunt L., in ‘t Veld S., Doecke J., Hok-A-Hin Y., Veverová K., Houtkamp I., Alcolea D., Halbgebauer S., Quesada C., Mattsson N., Martinez-Castillo M., López-Martínez M., Rábano A., Boonkamp L., Fowler C., Fortea J., Gaetani L., Toja A., Pijnenburg Y., Lemstra A., van der Flier W., Sánchez-Juan P., Hort J., Otto M., Anderl-Staub S., Sieben A., de Viel B., Engelborghs S., Hansson O., Masters C., Lleó A., Parnetti L., Teunissen C., del Campo M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Patient Stratification | Plasma |  Olink Explore 3072/384  Olink Focus |
Abstract
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.