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The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic\/inflammatory factors (ELISA). We then applied quantitative real\u2010time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected a statistically significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.000001) up\u2010regulation of Angiopoietin\u20102 (Ang\u20102) in CSF and stenotic middle cerebral arteries (RQ\u2009&gt;2) of MA patients compared to controls. A high Ang\u20102 plasma concentration (<jats:italic>p<\/jats:italic>\u2009=\u20090.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang\u20102 as diagnostic CSF biomarker (&gt;3741\u2009pg\/mL) and prognostic plasma biomarker (&gt;1162\u2009pg\/mL), to distinguish stable\u2010from\u2010progressive MA. Consistently, MA cellular model showed a significant up\u2010regulation (RQ\u2009&gt;2) of Ang\u20102 in RNF213 silenced condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results pointed out Ang\u20102 as a reliable biomarker mirroring arterial steno\u2010occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52076","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T09:15:06Z","timestamp":1713950106000},"page":"1590-1603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Angiopoietin\u20102 associates with poor prognosis in Moyamoya angiopathy"],"prefix":"10.1002","volume":"11","author":[{"given":"Gemma","family":"Gorla","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology and UCV, Neurology IX Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 20133 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