{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:40:26Z","timestamp":1782981626872,"version":"3.54.5"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The temporal ordering of biomarkers for cerebral amyloid angiopathy (CAA) is important for their use in trials and for the understanding of the pathological cascade of CAA. We investigated the presence and abnormality of the most common biomarkers in the largest (pre)symptomatic Dutch-type hereditary CAA (D-CAA) cohort to date.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We included cross-sectional data from participants with (pre)symptomatic D-CAA and controls without CAA. We investigated CAA-related cerebral small vessel disease markers on 3T-MRI, cerebrovascular reactivity with functional 7T-MRI (fMRI) and amyloid-\u03b2\n              <jats:sub>40<\/jats:sub>\n              and amyloid-\u03b2\n              <jats:sub>42<\/jats:sub>\n              levels in cerebrospinal fluid. We calculated frequencies and plotted biomarker abnormality according to age to form scatterplots.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              We included 68 participants with D-CAA (59% presymptomatic, mean age, 50 [range, 26\u201375] years; 53% women), 53 controls (mean age, 51 years; 42% women) for cerebrospinal fluid analysis and 36 controls (mean age, 53 years; 100% women) for fMRI analysis. Decreased cerebrospinal fluid amyloid-\u03b2\n              <jats:sub>40<\/jats:sub>\n              and amyloid-\u03b2\n              <jats:sub>42<\/jats:sub>\n              levels were the earliest biomarkers present: all D-CAA participants had lower levels of amyloid-\u03b2\n              <jats:sub>40<\/jats:sub>\n              and amyloid-\u03b2\n              <jats:sub>42<\/jats:sub>\n              compared with controls (youngest participant 30 years). Markers of nonhemorrhagic injury (&gt;20 enlarged perivascular spaces in the centrum semiovale and white matter hyperintensities Fazekas score, \u22652, present in 83% [n=54]) and markers of impaired cerebrovascular reactivity (abnormal BOLD amplitude, time to peak and time to baseline, present in 56% [n=38]) were present from the age of 30 years. Finally, markers of hemorrhagic injury were present in 64% (n=41) and only appeared after the age of 41 years (first microbleeds and macrobleeds followed by cortical superficial siderosis).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our results suggest that amyloid biomarkers in cerebrospinal fluid are the first to become abnormal in CAA, followed by MRI biomarkers for cerebrovascular reactivity and nonhemorrhagic injury and lastly hemorrhagic injury. This temporal ordering probably reflects the pathological stages of CAA and should be taken into account when future therapeutic trials targeting specific stages are designed.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.123.044688","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T10:00:25Z","timestamp":1709719225000},"page":"954-962","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Temporal Ordering of Biomarkers in Dutch-Type Hereditary Cerebral Amyloid Angiopathy"],"prefix":"10.1161","volume":"55","author":[{"given":"Emma A.","family":"Koemans","sequence":"first","affiliation":[{"name":"Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0953-7133","authenticated-orcid":true,"given":"Ingeborg","family":"Rasing","sequence":"additional","affiliation":[{"name":"Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-6676","authenticated-orcid":true,"given":"Sabine","family":"Voigt","sequence":"additional","affiliation":[{"name":"Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands."},{"name":"Radiology (S.V., T.W.v.H., M.R.S., M.J.v.P.O., M.A.A.v.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-9379","authenticated-orcid":true,"given":"Thijs W.","family":"van Harten","sequence":"additional","affiliation":[{"name":"Radiology (S.V., T.W.v.H., M.R.S., M.J.v.P.O., M.A.A.v.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4578-1376","authenticated-orcid":true,"given":"Reinier G.J.","family":"van der Zwet","sequence":"additional","affiliation":[{"name":"Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-6853","authenticated-orcid":true,"given":"Kanishk","family":"Kaushik","sequence":"additional","affiliation":[{"name":"Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-0997","authenticated-orcid":true,"given":"Manon R.","family":"Schipper","sequence":"additional","affiliation":[{"name":"Radiology (S.V., T.W.v.H., M.R.S., M.J.v.P.O., M.A.A.v.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-274X","authenticated-orcid":true,"given":"Nelleke","family":"van der Weerd","sequence":"additional","affiliation":[{"name":"Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5537-3179","authenticated-orcid":true,"given":"Erik W.","family":"van 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Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0635-7428","authenticated-orcid":true,"given":"Bea","family":"Kuiperij","sequence":"additional","affiliation":[{"name":"Department Neurology and Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen (B.K., M.M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-7876","authenticated-orcid":true,"given":"Marcel M.","family":"Verbeek","sequence":"additional","affiliation":[{"name":"Department Neurology and Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen (B.K., M.M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-6882","authenticated-orcid":true,"given":"Gisela M.","family":"Terwindt","sequence":"additional","affiliation":[{"name":"Departments of Neurology 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