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Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brain
Authors:Simpson Julie E  Wharton Stephen B  Cooper James  Gelsthorpe Catherine  Baxter Lynne  Forster Gillian  Shaw Pamela J  Savva George  Matthews Fiona E  Brayne Carol  Ince Paul G
Institution:Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
Abstract:White matter lesions (WML) are associated with dementia and are common in brain ageing. In order to determine whether alteration of the blood-brain barrier (BBB) may contribute to the pathogenesis of WML we assessed albumin leakage and expression of the tight junction (TJ) proteins claudin-5 (Cln-5), zona occludin-1 (ZO-1) and occludin in cases derived from the Medical Research Council Cognitive Function and Ageing Study. Albumin extravasation was widespread in the ageing brain and enhanced in WML, suggesting dysfunction of the BBB may contribute to the pathogenesis of WML. This was not accompanied by significant changes in the endothelial expression of TJ proteins. However, ZO-1 and occludin were expressed by glial cells throughout the parenchyma of both control white matter and WML, suggesting these TJ proteins may have other functions in the brain.
Keywords:White matter lesions  Blood–brain barrier  Tight junction proteins  Claudin-5  Occludin  ZO-1
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