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Currently, it is identified only at advanced stages due to the limitations of non-invasive diagnostic tools. Our pilot study evaluates metabolic and immune alterations in stroke patients with imaging-confirmed CAA. This prospective cohort study included stroke patients admitted to the University Hospital Erlangen with CAA diagnosis based on MRI findings. Metabolomic analysis of cerebrospinal fluid and serum samples was performed using liquid chromatography\/mass spectrometry, focusing on caffeine metabolism and amino acid pathways. Immunophenotyping of leukocytes was conducted via flow cytometry. The study included 22 stroke patients, of whom 10 had an MRI-based diagnosis of CAA. Metabolomic analysis revealed consistently lower levels of caffeine-related metabolites in CAA patients with significant differences in 5-acetylamino-6-amino-3-methyluracil, paraxanthine, theobromine, 3,7-dimethyluric acid, 3-methylxanthine and 1-methylxanthine. Amino acid levels showed no significant differences. Immunophenotyping revealed a reduction in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets, including effector and central memory T cells, alongside an increase in cytotoxic NK cells in CAA patients. These results suggest that specific metabolic and immune signatures could contribute to the development of diagnostic tools for the detection of CAA.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-31107-w","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:56:35Z","timestamp":1764939395000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomic and immunophenotypic signatures in cerebral amyloid angiopathy: a pilot study"],"prefix":"10.1038","volume":"15","author":[{"given":"Thanos","family":"Tsaktanis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Gessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Pfeuffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Farrenkopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike J.","family":"Naumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen A.","family":"Sembill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Fromm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Rothhammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji B.","family":"Kuramatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Mrochen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"31107_CR1","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1093\/brain\/awx047","volume":"140","author":"A Charidimou","year":"2017","unstructured":"Charidimou, A. et al. 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The authors confirm that all procedures performed in this study involving human participants were conducted in compliance with the ethical standards of with the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics declarations"}}],"article-number":"43262"}}