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

被引：79

作者：

Viggars, Andrew P. ^{[1
]}

Wharton, Stephen B. ^{[1
]}

Simpson, Julie E. ^{[1
]}

Matthews, Fiona E. ^{[2
]}

Brayne, Carol ^{[3
]}

Savva, George M. ^{[4
]}

Garwood, Claire ^{[1
]}

Drew, David ^{[1
]}

Shaw, Pamela J. ^{[1
]}

Ince, Paul G. ^{[1
]}

机构：

[1] Univ Sheffield, Sheffield Inst Translat Neurosci, Sheffield S10 2HQ, S Yorkshire, England

[2] Univ Cambridge, MRC Biostat Unit, Cambridge CB2 1TN, England

[3] Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge CB2 1TN, England

[4] Trinity Coll Dublin, Dept Med Gerontol, Dublin, Ireland

来源：

NEUROSCIENCE LETTERS | 2011年 / 505卷 / 01期

基金：

英国医学研究理事会;

关键词：

Blood brain barrier; Alzheimer's disease; Tight junction proteins; Brain ageing; MULTIPLE-SCLEROSIS; OXIDATIVE STRESS; DISEASE; PERMEABILITY; DEMENTIA; PROTEINS; WHITE; OLIGODENDROCYTE; ASTROCYTES; OCCLUDIN;

D O I：

10.1016/j.neulet.2011.09.049

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：25 / 30

页数：6

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