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

Neurosci Lett. 2011 Nov 7;505(1):25-30. doi: 10.1016/j.neulet.2011.09.049. Epub 2011 Sep 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Albumins
  • CLDN5 protein, human
  • Claudin-5
  • Claudins
  • Collagen Type IV
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Fibrinogen