Journal Article DZNE-2026-00880

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

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2026
Nature Research London

Nature aging 6(8), 1717 - 1732 () [10.1038/s43587-026-01162-7]

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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.

Keyword(s): Humans (MeSH) ; Biomarkers: blood (MeSH) ; Diagnosis, Differential (MeSH) ; Proteomics: methods (MeSH) ; Proteome: metabolism (MeSH) ; Female (MeSH) ; Male (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Alzheimer Disease: blood (MeSH) ; Aged (MeSH) ; Frontotemporal Dementia: diagnosis (MeSH) ; Frontotemporal Dementia: blood (MeSH) ; Neurodegenerative Diseases: diagnosis (MeSH) ; Neurodegenerative Diseases: blood (MeSH) ; Lewy Body Disease: diagnosis (MeSH) ; Lewy Body Disease: blood (MeSH) ; Glial Fibrillary Acidic Protein: blood (MeSH) ; Dementia: diagnosis (MeSH) ; Dementia: blood (MeSH) ; Cohort Studies (MeSH) ; Biomarkers ; Proteome ; Glial Fibrillary Acidic Protein

Classification:

Contributing Institute(s):
  1. Clinical Study Center (Ulm) (Clinical Study Center (Ulm))
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Essential Science Indicators ; IF >= 15 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2026-08-17, last modified 2026-09-10