Alterations of the blood–brain barrier in cerebral white matter lesions in the ageing brain

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.

Research highlights▶ Blood–brain barrier (BBB) dysfunction is widespread in the ageing brain. ▶ Age-related white matter lesions showed high levels of serum plasma extravasation. ▶ BBB dysfunction was not associated with changes in tight junction protein expression. ▶ Occludin and ZO-1 were expressed by glial cells in the ageing brain.