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

doi:10.1016/j.neulet.2011.09.049

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

Norwich Epidemiology Centre

Research output: Contribution to journal › Article › peer-review

79 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 language	English
Pages (from-to)	25-30
Number of pages	6
Journal	Neuroscience Letters
Volume	505
Issue number	1
DOIs	https://doi.org/10.1016/j.neulet.2011.09.049
Publication status	Published - 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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10.1016/j.neulet.2011.09.049

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Viggars, A. P., Wharton, S. B., Simpson, J. E., Matthews, F. E., Brayne, C., Savva, G. M., Garwood, C., Drew, D., Shaw, P. J., & Ince, P. G. (2011). 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. Neuroscience Letters, 505(1), 25-30. https://doi.org/10.1016/j.neulet.2011.09.049

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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.",

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Viggars, AP, Wharton, SB, Simpson, JE, Matthews, FE, Brayne, C, Savva, GM, Garwood, C, Drew, D, Shaw, PJ & Ince, PG 2011, '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', Neuroscience Letters, vol. 505, no. 1, pp. 25-30. https://doi.org/10.1016/j.neulet.2011.09.049

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AU - Matthews, Fiona E

AU - Brayne, Carol

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AU - Garwood, Claire

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AU - Shaw, Pamela J

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AB - 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.

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KW - Disease Progression

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KW - Female

KW - Fibrinogen

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KW - Male

KW - Membrane Proteins

KW - Occludin

KW - Phosphoproteins

KW - Statistics, Nonparametric

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VL - 505

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JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

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