title: Circulating Biomarkers in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patients.
abstract: BACKGROUND
  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy presenting with variable features, including migraine, psychiatric disorders, stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL is characterized by leukoencephalopathy, multiple lacunar infarcts, and microbleeds. Previous studies suggest a possible role of endothelial impairment in the pathogenesis of the disease.
  
  
  METHODS
  We assessed plasma levels of von Willebrand factor (vWF) and thrombomodulin (TM) and the blood levels of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in 49 CADASIL patients and 49 age-matched controls and their association with clinical/functional and neuroimaging features.
  
  
  RESULTS
  In multivariate analysis, CADASIL patients had significantly higher vWF and lower EPC levels. TM levels were similar in the 2 groups. CADASIL patients with a more severe clinical phenotype (history of stroke or dementia) presented lower CPC levels in comparison with patients with a milder phenotype. On correlation analysis, lower CPC levels were associated with worse performances on neuropsychological, motor and functional tests, and with higher lesion load on brain magnetic resonance imaging (degree of leukoencephalopathy and number of lacunar infarcts).
  
  
  CONCLUSIONS
  This is the first CADASIL series in which multiple circulating biomarkers have been studied. Our findings support previous studies on the presence and the possible modulating effect of endothelial impairment in the disease. Furthermore, our research data suggest that blood CPCs may be markers of disease severity.
authors.affiliation: Emergency Department, Stroke Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pescini
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Donnini
authors.affiliation: Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cesari
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy; Department of Emergency Neurology, C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Nannucci
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Valenti
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rinnoci
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Poggesi
authors.affiliation: Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Don Carlo Gnocchi IRCCS Foundation, Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.affiliation: Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.affiliation: Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Rogolino
authors.affiliation: Department of Medical Surgical and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carluccio
authors.affiliation: Department of Medical Surgical and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Department of Medical Surgical and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.affiliation: Department of Medical Surgical and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Balestrino
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Adriano
authors.affiliation: Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy; Institute of Neuroscience, Italian National Research Council, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.affiliation: NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy. Electronic address: leonardo.pantoni@unifi.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D046589:CADASIL / Q000097:blood* / Q000473:pathology*; D016022:Case-Control Studies; D066026:Endothelial Progenitor Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D018180:Thrombomodulin / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C546931:THBD protein, human; D018180:Thrombomodulin; D014841:von Willebrand Factor; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: CADASIL; cerebral small vessel disease; circulating progenitor cells; endothelial impairment; von Willebrand factor