Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort

Andrew P Viggars, Stephen B Wharton, Julie E Simpson, Fiona E Matthews, Carol Brayne, George M Savva, Claire Garwood, David Drew, Pamela J Shaw, Paul G Ince

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    62 Citations (Scopus)

    Abstract

    Impairment of the blood brain barrier (BBB) in human brain ageing and its relationship to Alzheimer-type pathology remains poorly defined. We have investigated the BBB in temporal cortex of brain donations from a population-representative sample of 92 participants from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), a longitudinal study with a programme of brain donation. BBB alteration was investigated by immunohistochemistry to albumin and fibrinogen and to the tight junction proteins claudin-5, zonula occludens-1 (ZO-1) and occludin. BBB leakage showed wide population-variation and increased with progression of Alzheimer-type pathology, though with considerable overlap between different levels of Alzheimer-type pathology. This was accompanied by increased mean vascular density, but not by down-regulation of tight junction proteins. ZO-1 and occludin were also expressed in glia. Mechanisms leading to BBB leakage in brain ageing remain to be defined, but the population-variation in BBB changes and its early increase in relationship to Alzheimer-type pathology progression suggest that BBB dysfunction contributes to brain ageing.
    Original languageEnglish
    Pages (from-to)25-30
    Number of pages6
    JournalNeuroscience Letters
    Volume505
    Issue number1
    DOIs
    Publication statusPublished - 7 Nov 2011

    Keywords

    • Aged
    • Aged, 80 and over
    • Aging
    • Albumins
    • Blood-Brain Barrier
    • Cerebral Cortex
    • Claudin-5
    • Claudins
    • Cohort Studies
    • Collagen Type IV
    • Disease Progression
    • Down-Regulation
    • Female
    • Fibrinogen
    • Humans
    • Male
    • Membrane Proteins
    • Occludin
    • Phosphoproteins
    • Statistics, Nonparametric
    • Zonula Occludens-1 Protein

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