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Modern diagnosis of sCAA relies on radiological detection of late-stage hallmarks of disease, complicating early diagnosis and potential interventions in disease progression. Our goal in this study was to identify and validate novel biomarkers for sCAA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a proximity extension assay (PEA) on cerebrospinal fluid (CSF) samples of sCAA\/control participants (<jats:italic>n<\/jats:italic>\u2009=\u200934\/51). Additionally, we attempted to validate the top candidate biomarker in CSF and serum samples (<jats:italic>n<\/jats:italic>\u2009=\u200938\/26) in a largely overlapping validation cohort, through analysis with a targeted immunoassay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Thirteen proteins were differentially expressed through PEA, with top candidate NFL significantly increased in CSF of sCAA patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Validation analyses using immunoassays revealed increased CSF and serum NFL levels in sCAA patients (both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) with good discrimination between sCAA and controls (AUC: 0.85; AUC: 0.79 respectively). Additionally, the CSF: serum NFL ratio was significantly elevated in sCAA (<jats:italic>p<\/jats:italic>\u2009=\u20090.002).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>Large-scale targeted proteomics screening of CSF of sCAA patients and controls identified thirteen biomarker candidates for sCAA. Orthogonal validation of NFL identified NFL in CSF and serum as biomarker, capable of differentiating between sCAA patients and controls.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-024-01473-0","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T09:02:15Z","timestamp":1715677335000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Proximity extension assay in cerebrospinal fluid identifies neurofilament light chain as biomarker of neurodegeneration in sporadic cerebral amyloid angiopathy"],"prefix":"10.1186","volume":"16","author":[{"given":"Marc","family":"Vervuurt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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Proteomics. 2014;14(13\u201314):1587\u201392.","journal-title":"Proteomics"}],"container-title":["Alzheimer's Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-024-01473-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13195-024-01473-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-024-01473-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T09:07:10Z","timestamp":1715677630000},"score":1,"resource":{"primary":{"URL":"https:\/\/alzres.biomedcentral.com\/articles\/10.1186\/s13195-024-01473-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1473"],"URL":"https:\/\/doi.org\/10.1186\/s13195-024-01473-0","relation":{},"ISSN":["1758-9193"],"issn-type":[{"value":"1758-9193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,14]]},"assertion":[{"value":"21 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Lumbar punctures were performed after informed consent from the patients themselves or from the patients\u2019 legal representatives. Most participants underwent lumbar punctures in the context of cohort studies on biomarkers. All sCAA patients were included from the CAVIA (no. 733,050,202) and BIONIC (nr. 733,050,822) studies. Most control participants were included from the CAFE study (nr. 5R01NS104147-02), while some were included in the context of a routine diagnostic clinical work-up. This study was approved by the Medical Ethics Committee Arnhem-Nijmegen.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"108"}}