- April 14, 2026
- Chotima Böttcher, et al., Charité – Universitätsmedizin Berlin
Topic/Product:
CNS Disease Panel 120
Disease Area:
Alzheimer's Disease
Sample Type:
CSF
Abstract
INTRODUCTION
Tryptophan metabolism is increasingly implicated in Alzheimer’s disease (AD), particularly through aryl hydrocarbon receptor (AhR) ligands that influence neuroinflammation. However, their relationships with core AD pathology—amyloid-β (A) and tau (T) deposition—and associated immune–proteomic alterations remain unclear.
METHODS
We performed integrative multi-omics/high-dimensional profiling of cerebrospinal fluid (CSF) and peripheral blood from A-T- (n = 19) and A+T+ (n = 35) individuals, classified based on CSF Aβ and pTau181 levels. Analyses included targeted metabolomics, mass cytometry, and NULISA-based proteomics, and inter-compartmental correlation analysis. Brain-derived tryptophan catabolism was investigated using single-nucleus RNA sequencing (snRNA-seq).
RESULTS
Thirteen differentially expressed CSF proteins in A+T+ individuals correlated positively with tryptophan metabolites and pyroglutamate, and negatively with regulatory T cells, isobutyrate, and dendritic cells. Similar patterns were observed in blood. snRNA-seq suggested partial brain origin of metabolites.
DISCUSSION
Our findings highlight conserved immune–metabolic–proteomic signatures in AD and implicate tryptophan metabolism as a cross-compartmental factor relevant for biomarker and therapeutic development.
Highlights
- Thirteen cerebrospinal fluid (CSF) proteins involved in metabolism and neuronal function link to Alzheimer’s disease (AD) pathology
- Intergrative analysis reveals shared and compartment-specific AD signatures
- Tryptophan-kynurenine metabolites correlate with AD pathology
- Indole metabolites show CSF-plasma coupling in A+T+ individuals
- Immune signatures diverge across CSF (regulatory T cells [Tregs], dendritic cells [DCs]) and blood (B and myeloid cells)
Authors & Affiliations
Meng Wang¹², Maria Buthut³⁴, Jenny Meinhardt⁵, Carolin Otto³, Gerardina Gallaccio¹², Camila Fernández-Zapata¹²⁶⁷, Matteo Teves⁸, Claudia Samol⁸, Katja Dettmer⁸, Simon Heckscher⁸, Sakshi Kamboj⁸, Yozlem Bahar⁵⁹, Christian Conrad¹⁰, Christian Böttcher¹², Desiree Kunkel¹¹, Klemens Ruprecht³, Friedemann Paul¹²³¹², Peter J. Oefner⁸, Helena Radbruch⁵, Wolfram Gronwald⁸, Harald Prüß³⁴, and Chotima Böttcher¹²
¹ Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin Berlin, Berlin, Germany
² Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
³ Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany
⁴ German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
⁵ Department of Neuropathology, Charité – Universitätsmedizin Berlin, Berlin, Germany
⁶ III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
⁷ Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
⁸ Institute of Functional Genomics, University of Regensburg, Regensburg, Germany
⁹ Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin, Germany
¹⁰ Center of Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
¹¹ Flow & Mass Cytometry Core Facility, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
¹² Neuroscience Research Center, Charité – Universitätsmedizin Berlin, Berlin, Germany