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

Bellomo, Giovanni ; Vermunt, Lisa ; in ‘t Veld, Sjors ; Doecke, James D. ; Hok-A-Hin, Yanaika S. ; Veverová, Kateřina ; Houtkamp, Isabel M. ; Alcolea, Daniel ; Halbgebauer, Steffen and Quesada, Carlos , et al. (2026) In Nature Aging 6(8). p.1717-1732
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Aging
volume
6
issue
8
pages
16 pages
publisher
Springer
external identifiers
  • scopus:105045295500
  • pmid:42477094
ISSN
2662-8465
DOI
10.1038/s43587-026-01162-7
language
English
LU publication?
yes
id
7910e9ed-abf9-4920-b823-05cc10ddc6fd
date added to LUP
2026-09-25 14:05:31
date last changed
2026-10-10 13:05:07
@article{7910e9ed-abf9-4920-b823-05cc10ddc6fd,
  abstract     = {{<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 (n = 805). These findings support plasma proteomics as an approach for biomarker-based differential diagnosis and disease staging across major neurodegenerative dementias.</p>}},
  author       = {{Bellomo, Giovanni and Vermunt, Lisa and in ‘t Veld, Sjors and Doecke, James D. and Hok-A-Hin, Yanaika S. and Veverová, Kateřina and Houtkamp, Isabel M. and Alcolea, Daniel and Halbgebauer, Steffen and Quesada, Carlos and Mattsson, Niklas and Martinez-Castillo, Minerva and López-Martínez, María José and Rábano, Alberto and Boonkamp, Lynn and Fowler, Christopher and Fortea, Juan and Gaetani, Lorenzo and Toja, Andrea and Pijnenburg, Yolande and Lemstra, Afina and van der Flier, Wiesje M. and Sánchez-Juan, Pascual and Hort, Jakub and Otto, Markus and Anderl-Staub, Sarah and Sieben, Anne and de Viel, Bart and Engelborghs, Sebastiaan and Hansson, Oskar and Masters, Colin and Lleó, Alberto and Parnetti, Lucilla and Teunissen, Charlotte E. and del Campo, Marta}},
  issn         = {{2662-8465}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1717--1732}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{Plasma proteome profiling identified biomarkers for the differential diagnosis and molecular staging of neurodegenerative dementias}},
  url          = {{http://dx.doi.org/10.1038/s43587-026-01162-7}},
  doi          = {{10.1038/s43587-026-01162-7}},
  volume       = {{6}},
  year         = {{2026}},
}