• Neurology · Jan 2017

    β-Amyloid in CSF: Biomarker for preclinical cerebral amyloid angiopathy.

    • Ellis S van Etten, Marcel M Verbeek, Jeroen van der Grond, Ronald Zielman, Sanneke van Rooden, Erik W van Zwet, Anna M van Opstal, Joost Haan, Steven M Greenberg, Mark A van Buchem, Marieke J H Wermer, and Gisela M Terwindt.
    • From the Departments of Neurology (E.S.v.E., R.Z., J.H., M.J.H.W., G.M.T.), Radiology (J.v.d.G., S.v.R., A.M.v.O., M.A.v.B.), and Biostatistics (E.W.v.Z.), Leiden University Medical Center; Departments of Neurology and Laboratory Medicine (M.M.V.), Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen; Department of Neurology (J.H.), Alrijne Hospital, Leiderdorp, the Netherlands; and J. Philip Kistler Stroke Research Center (S.M.G.), Massachusetts General Hospital, Boston. e.s.van_etten@lumc.nl.
    • Neurology. 2017 Jan 10; 88 (2): 169-176.

    ObjectiveTo investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the earliest deposited form of β-amyloid (Aβ).MethodsHCHWA-D mutation carriers and controls were enrolled in the cross-sectional EDAN (Early Diagnosis of Amyloid Angiopathy Network) study. The HCHWA-D group was divided into symptomatic carriers with a previous intracerebral hemorrhage and presymptomatic carriers. CSF concentrations of Aβ40, Aβ42, total tau, and phosphorylated tau181 proteins were compared to those of controls of a similar age. Correlations between CSF biomarkers, MRI markers, and age were investigated with multivariate linear regression analyses.ResultsWe included 10 symptomatic patients with HCHWA-D (mean age 55 ± 6 years), 5 presymptomatic HCHWA-D carriers (mean age 36 ± 13 years), 31 controls <50 years old (mean age 31 ± 7 years), and 50 controls ≥50 years old (mean age 61 ± 8 years). After correction for age, CSF Aβ40 and Aβ42 were significantly decreased in symptomatic carriers vs controls (median Aβ40 1,386 vs 3,867 ng/L, p < 0.001; median Aβ42 289 vs 839 ng/L, p < 0.001) and in presymptomatic carriers vs controls (median Aβ40 3,501 vs 4,684 ng/L, p = 0.011; median Aβ42 581 vs 1,058 ng/L, p < 0.001). Among mutation carriers, decreasing CSF Aβ40 was associated with higher lobar microbleed count (p = 0.010), increasing white matter hyperintensity volume (p = 0.008), and presence of cortical superficial siderosis (p = 0.02).ConclusionsDecreased levels of CSF Aβ40 and Aβ42 occur before HCHWA-D mutation carriers develop clinical symptoms, implicating vascular deposition of both Aβ species as early steps in cerebral amyloid angiopathy pathogenesis. CSF Aβ40 and Aβ42 may serve as preclinical biomarkers of cerebral amyloid angiopathy pathology.© 2016 American Academy of Neurology.

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