Regional blood‐brain barrier breakdown and Alzheimer’s disease pathology in aging

Abstract

AbstractBackgroundAlthough blood‐brain barrier disruption (BBBd) is described in aging and AD, its regional characteristics and relationship with AD pathology have not been fully characterized. We aimed to determine whether there are age‐related regional differences in BBBd in cognitively normal adults and if regional BBBd is related to Aβ, tau, and neurodegeneration.MethodBBBd was measured using DCE‐MRI in 9 older adults (OA; 78±6 years, 7M) and 10 young adults (YA; 24±2 years, 7M). The Patlak model was used to generate BBB permeability volume transfer constant (Ktrans) maps in FreeSurfer regions of interest (ROIs). In the OA, PiB‐PET was used to measure global amyloid burden, FTP‐PET to measure tau in medial temporal lobe (MTL) regions, and T1 MRI to measure cortical thickness. We conducted repeated measures ANOVA (group, region, and group x region) with post‐hoc tests to investigate regional differences in Ktrans values between OA/YA and Aβ+/Aβ‐. Linear regressions were used to evaluate the relationships of tau and thickness with Ktrans.ResultsThere was a significant region by age interaction (p< 0.001). OA had greater Ktrans than YA in the entorhinal cortex, parahippocampus, cuneus, fusiform, inferior temporal gyrus (IT), and the lateral occipital cortex (independent sample t‐tests, ps < 0.05; Fig 1). YA had greater Ktrans in the superior and transverse temporal lobe (ps <0.05). In the OA, a trend‐level region by Aβ status interaction (p=0.09) was found for the same ROIs (Fig 2). There were no significant relationships between MTL tau and Ktrans. There was a significant negative relationship between thickness and Ktrans in an averaged ROI consisting of the six regions where OA showed greater Ktrans than YA (p=0.025; Fig 3).ConclusionThese findings show that greater BBBd in OA is relatively specific to the MTL and IT, which are regions affected early in AD. They also suggest that increased BBBd in these regions may be related to amyloid accumulation and neurodegeneration. These findings require extension in larger samples, but implies BBBd as a potentially important event in aging and in the pathophysiology of AD.