Alzheimer's disease pathology is associated with earlier alterations to blood-brain barrier water permeability compared with healthy ageing in TgF344-AD rats

Abstract

The effects of Alzheimer's disease (AD) and ageing on blood-brain barrier (BBB) breakdown are investigated in TgF344-AD and wild-type rats aged 13, 18 and 21 months. Permeability surface area products of the BBB to water (PS_w ) and gadolinium-based contrast agent (PS_g ) were measured in grey matter using multiflip angle multiecho dynamic contrast-enhanced MRI. At 13 months of age, there was no significant difference in PS_w between TgF344-AD and wild-types (p = 0.82). Between 13 and 18 months, PS_w increased in TgF344-AD rats (p = 0.027), but not in wild-types (p = 0.99), leading to significantly higher PS_w in TgF344-AD rats at 18 months, as previously reported (p = 0.012). Between 18 and 21 months, PS_w values increased in wild-types (p = 0.050), but not in TgF344-AD rats (p = 0.50). These results indicate that BBB water permeability is affected by both AD pathology and ageing, but that changes occur earlier in the presence of AD pathology. There were no significant genotype or ageing effects on PS_g (p > 0.05). In conclusion, we detected increases in BBB water permeability with age in TgF344-AD and wild-type rats, and found that changes occurred at an earlier age in rats with AD pathology.

Keywords: ageing, Alzheimer's disease, BBB breakdown, BBB dysfunction, BBB permeability, blood-brain barrier, MRI, TgF344-AD.