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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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
Issue number1
Publication statusPublished - 7 Nov 2011


  • 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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