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| Item Type: | Article |
|---|---|
| Title: | Immune–proteo–metabolomic changes link to Aβ and tau pathology in Alzheimer disease |
| Creators Name: | Wang, Meng, Buthut, Maria, Meinhardt, Jenny, Otto, Carolin, Gallaccio, Gerardina, Fernández-Zapata, Camila, Teves, Matteo, Samol, Claudia, Dettmer, Katja, Heckscher, Simon, Kamboj, Sakshi, Bahar (Landthaler), Yozlem, Conrad, Christian, Böttcher, Christian, Kunkel, Desiree, Ruprecht, Klemens, Paul, Friedemann, Oefner, Peter J., Radbruch, Helena, Gronwald, Wolfram, Prüß, Harald and Böttcher, Chotima |
| 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. |
| Keywords: | Alzheimer’s Disease, Amyloid-Beta, Aryl Hydrocarbon Receptor, Mass Cytometry, Tau Pathology, Tryptophan |
| Source: | Alzheimer's & Dementia |
| ISSN: | 1552-5260 |
| Publisher: | Wiley / Alzheimer's Association |
| Volume: | 22 |
| Number: | 4 |
| Page Range: | e71359 |
| Date: | April 2026 |
| Official Publication: | https://doi.org/10.1002/alz.71359 |
| PubMed: | View item in PubMed |
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