Journal Article

DZNE-2026-00305

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Microglia protein profiles in CSF across Alzheimer's disease clinical stages.

Blujdea, E.-R. ; van Bokhoven, P. ; Martino-Adami, P. V. ; Marshe, V. S. ; Vromen, E. M. ; Hok-A-Hin, Y. S. ; Boiten, W. A. ; Irwin, D. J. ; Chen-Plotkin, A. S. ; Lemstra, A. W. ; Pijnenburg, Y. ; van der Flier, W. M. ; Peters, O.DZNE* ; Hellmann-Regen, J.DZNE* ; Priller, J.DZNE* ; Schneider, A.DZNE* ; Wiltfang, J.DZNE* ; Jessen, F.DZNE* ; Düzel, E.DZNE* ; Buerger, K.DZNE* ; Perneczky, R.DZNE* ; Teipel, S.DZNE* ; Laske, C.DZNE* ; Brosseron, F.DZNE* ; Consortium, D. (Collaboration Author) ; Del Campo, M. ; Wijdeven, R. ; Visser, P.-J. ; Tijms, B. M. ; De Jager, P. L. ; Ramirez, A.DZNE* ; Teunissen, C. E. ; Vermunt, L. ; Preis, L. (Contributor)Extern* ; Gref, D. (Contributor)Extern* ; Spruth, E. J. (Contributor)Extern* ; Gemenetzi, M. (Contributor)Extern* ; Fließbach, K. (Contributor)Extern* ; Bartels, C. (Contributor) ; Rostamzadeh, A. (Contributor) ; Glanz, W. (Contributor)Extern* ; Incesoy, E. (Contributor)Extern* ; Janowitz, D. (Contributor)Extern* ; Ewers, M. (Contributor) ; Rauchmann, B. S. (Contributor)Extern* ; Kilimann, I. (Contributor)Extern* ; Görß, D. (Contributor)Extern* ; Sodenkamp, S. (Contributor)Extern* ; Spottke, A. (Contributor)Extern* ; Kronmüller, M. T. (Contributor)Extern* ; Wagner, M. (Contributor)Extern* ; Röske, S. (Contributor)Extern*

2026
Nature Research London

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s43587-026-01088-0

Abstract: Microglia are implicated in the progression of Alzheimer's disease (AD) pathology from its earliest stages, suggesting that cerebrospinal fluid (CSF) microglia profiling across clinical AD stages can aid in treatment development and monitoring. We analyzed two CSF cohorts (n = 834) that span from unimpaired controls to preclinical and dementia AD stages, identifying 109 dysregulated microglia-related proteins. Enrichment analyses revealed innate immune processes and cellular recruitment in preclinical AD, whereas AD dementia revealed adaptive immunity and macrophage responses. Next, we aligned the in vivo microglia protein profiles with ex vivo-derived microglial transcriptomic signatures, such as disease-associated microglia phenotypes. Transcriptomic signatures were not specific to either clinical stage but spanned both. We classified an 18-protein panel highlighting distinct changes between the preclinical and dementia stages. Our findings underscore the potential of microglia-based biomarker research for AD staging, offering insights into microglia dynamics in clinical AD stages and how transcriptomic signatures translate to proteomic profiles.

Keyword(s): Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: immunology (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Humans (MeSH) ; Microglia: metabolism (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Male (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Transcriptome (MeSH) ; Aged, 80 and over (MeSH) ; Disease Progression (MeSH) ; Proteomics (MeSH) ; Middle Aged (MeSH) ; Biomarkers

---

Contributing Institute(s):

1. Biomarker-Assisted Early Detection of Dementias (AG Peters)
2. Interdisciplinary Dementia Research (AG Endres)
3. Astrocyte - Synapse Interactions (AG Ackermann)
4. Translational Dementia Research (Bonn) (AG Schneider)
5. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
6. Clinical Alzheimer’s Disease Research (AG Jessen)
7. Clinical Neurophysiology and Memory (AG Düzel)
8. Clinical Research (Munich) (Clinical Research (Munich))
9. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
10. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
11. Parkinson Genetics (AG Gasser)
12. Neuroinflammation, Biomarker (AG Heneka)
13. Patient Studies (Bonn) (Patient Studies (Bonn))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)

Experiment(s):

1. Longitudinal Cognitive Impairment and Dementia Study

Appears in the scientific report 2026

---

Database coverage:
; ; ; 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

---