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Low Cerebrospinal Fluid Sulfatide Predicts Progression of White Matter Lesions - The LADIS Study

Journal article
Authors Michael Jonsson
Henrik Zetterberg
Sindre Rolstad
Åke Edman
A. A. Gouw
Maria Bjerke
Karin Lind
Kaj Blennow
L. Pantoni
D. Inzitari
Anders Wallin
Published in Dementia and Geriatric Cognitive Disorders
Volume 34
Issue 1
Pages 61-67
ISSN 1420-8008
Publication year 2012
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 61-67
Language en
Links dx.doi.org/10.1159/000341576
Keywords Leukoaraiosis, Progression, Cerebrospinal fluid, Biomarkers, Oligodendrocyte, Myelin, Sulfatide, subcortical vascular dementia, normal-pressure hydrocephalus, mild, cognitive impairment, neurofilament protein, cns remyelination, leukoaraiosis, disability, hyperintensities, disease, brain
Subject categories Neurology, Neurochemistry, Neuroscience

Abstract

Background/Aims: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. Methods: CSF from elderly individuals with WML was analyzed for amyloid markers, total tau, hyperphosphorylated t, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). Results: 37 subjects (age 73.6 +/- 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). Conclusion: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.

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