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Transforming growth factor \u03b21 (TGF\u03b21) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore, we investigated whether the TGF\u03b2 pathway is involved in HCHWA\u2010D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Components of the TGF\u03b2 pathway were analyzed with quantitative RT\u2010PCR. TGF\u03b21 and TGF\u03b2 Receptor 2 (TGFBR2) gene expression levels were significantly increased in HCHWA\u2010D in comparison to the controls, in both frontal and occipital lobes. TGF\u03b2\u2010induced pro\u2010fibrotic target genes were also upregulated. We further assessed pathway activation by detecting phospho\u2010SMAD2\/3 (pSMAD2\/3), a direct TGF\u03b2 down\u2010stream signaling mediator, using immunohistochemistry. We found abnormal pSMAD2\/3 granular deposits specifically on HCHWA\u2010D angiopathic frontal and occipital vessels. We graded pSMAD2\/3 accumulation in angiopathic vessels and found a positive correlation with the CAA load independent of the brain area. We also observed pSMAD2\/3 granules in a halo surrounding occipital vessels, which was specific for HCHWA\u2010D. The result of this study indicates an upregulation of TGF\u03b21 in HCHWA\u2010D, as was found previously in AD with CAA pathology. We discuss the possible origins and implications of the TGF\u03b2 pathway deregulation in the microvasculature in HCHWA\u2010D. These findings identify the TGF\u03b2 pathway as a potential biomarker of disease progression and a possible target of therapeutic intervention in HCHWA\u2010D.<\/jats:p>","DOI":"10.1111\/bpa.12533","type":"journal-article","created":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T23:52:46Z","timestamp":1496101966000},"page":"495-506","source":"Crossref","is-referenced-by-count":19,"title":["TGF\u03b2 pathway deregulation and abnormal phospho\u2010SMAD2\/3 staining in hereditary cerebral hemorrhage with amyloidosis\u2010Dutch type"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8696-7145","authenticated-orcid":false,"given":"Laure","family":"Grand Moursel","sequence":"first","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center Leiden the Netherlands"},{"name":"Department of Radiology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon P.","family":"Munting","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center Leiden the Netherlands"},{"name":"Department of Radiology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"van der Graaf","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center Leiden the Netherlands"},{"name":"Department of Radiology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd G.","family":"van Duinen","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Jose T. 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