title: 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.
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.
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, 385A Glossop Road, Sheffield S102HQ, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Viggars
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wharton
authors.forename: Julie E
authors.initials: JE
authors.lastname: Simpson
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Matthews
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
authors.forename: George M
authors.initials: GM
authors.lastname: Savva
authors.forename: Claire
authors.initials: C
authors.lastname: Garwood
authors.forename: David
authors.initials: D
authors.lastname: Drew
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ince
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000418:Albumins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology*; D062507:Claudin-5; D057167:Claudins / Q000378:metabolism; D015331:Cohort Studies; D024141:Collagen Type IV / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D018709:Statistics, Nonparametric; D062826:Zonula Occludens-1 Protein
chemical_list: D000418:Albumins; C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; D024141:Collagen Type IV; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005340:Fibrinogen