Premium
Age‐associated changes in the blood‐brain barrier: comparative studies in human and mouse
Author(s) -
Goodall E. F.,
Wang C.,
Simpson J. E.,
Baker D. J.,
Drew D. R.,
Heath P. R.,
Saffrey M. J.,
Romero I. A.,
Wharton S. B.
Publication year - 2018
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12408
Subject(s) - astrogliosis , ageing , pathology , cerebellum , glial fibrillary acidic protein , cortex (anatomy) , astrocyte , human brain , cerebellar cortex , pericyte , cerebral cortex , biology , blood–brain barrier , gliosis , endocrinology , immunohistochemistry , medicine , central nervous system , neuroscience , endothelial stem cell , biochemistry , in vitro
Aims While vascular pathology is a common feature of a range of neurodegenerative diseases, we hypothesized that vascular changes occur in association with normal ageing. Therefore, we aimed to characterize age‐associated changes in the blood–brain barrier ( BBB ) in human and mouse cohorts. Methods Immunohistochemistry and Evans blue assays were used to characterize BBB dysfunction (tight junction protein expression and serum plasma protein accumulation), vascular pathology (pericyte loss and vascular density) and glial pathology (astrocyte and microglial density) in ageing neurological control human prefrontal cortex (a total of 23 cases from 5 age groups representing the spectrum of young adult to old age: 20–30 years, 31–45 years, 46–60 years, 61–75 years and 75+) and C57 BL /6 mice (3 months, 12 months, 18 months and 24 months, n = 5/6 per group). Results Quantification of the tight junction protein ZO ‐1 within the cortex and cerebellum of the mouse cohort showed a significant trend to both increased number (cortex P < 0.001, cerebellum P < 0.001) and length (cortex P < 0.001, cerebellum P < 0.001) of junctional breaks associated with increasing age. GFAP expression significantly correlated with ageing in the mice ( P = 0.037). In the human cohort, assessment of human protein accumulation (albumin, fibrinogen and human IgG) demonstrated cells morphologically resembling clasmatodendritic astrocytes, indicative of BBB dysfunction. Semiquantitative assessment of astrogliosis in the cortex expression revealed an association with age ( P = 0.003), while no age‐associated changes in microglial pathology, microvascular density or pericyte coverage were detected. Conclusions This study demonstrates BBB dysfunction in normal brain ageing, both in human and mouse cohorts.