Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology

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 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 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 Viggars et al  This paper investigates the blood brain barrier in a population representative ageing brain cohort from the MRC Cognitive Function and Ageing Study  There is population-variation in blood brain barrier leakage, determined by immunohistochemistry for albumin.  Blood brain barrier leakage was seen at early stages of Alzheimer-type pathology and increased with increasing Alzheimer-type pathology.  Blood brain barrier leakage was not accompanied by down-regulation of tight junction proteins. 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.