Michael Heming MD, Anna-Lena Börsch MSc, Simone Melnik MSc, Noemi Gmahl MD, Louisa Müller-Miny MD, Christine Dambietz MD, Lukas Fisch MSc, Timm Kühnel MSc, Tobias J. Brix PhD, Alice Janssen MSc, Eva Schumann MSc, Catharina C. Gross PhD, Julian Varghese MD, Tim Hahn PhD, Heinz Wiendl MD, Gerd Meyer zu Hörste MD
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引用次数: 0
Abstract
Objective
Cerebrospinal fluid (CSF) provides unique insights into the brain and neurological diseases. However, the potential of CSF flow cytometry applied on a large scale remains unknown.
Methods
We used data-driven approaches to analyze paired CSF and blood flow cytometry measurements from 8,790 patients (discovery cohort) and CSF only data from 3,201 patients (validation cohort) collected across neurological diseases in a real-world setting.
Results
In somatoform controls (n = 788), activation of T cells increased with age in both CSF and blood, whereas double negative blood T cells (CD3+CD4−CD8−) decreased with age. A machine learning model of CSF and blood immune cells defined immune age, which correlated strongly with true biological age (r = 0.71). Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative. This clustering was validated in an analytically independent test dataset (8,790 patients) and in a temporally independent cohort (3,201 patients). Patients with multiple sclerosis were more likely to have progressive disease when assigned to the neurodegeneration cluster and to have lower disability in the autoimmune cluster. Patients with dementia in the neurodegeneration cluster showed more severe disease progression. Flow cytometry helped differentiate dementia from controls, thereby enhancing the diagnostic power of routine CSF diagnostics.
Interpretation
Flow cytometry of CSF and blood thus identifies site-specific aging patterns and disease-overarching patterns of neurodegeneration. ANN NEUROL 2025;97:779–790
期刊介绍:
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.