Associations between regional blood-brain barrier disruption, aging, and Alzheimer’s disease biomarkers in cognitively normal older adults

Abstract

AbstractBackgroundBlood-brain barrier disruption (BBBd) has been hypothesized as a feature of aging that may lead to the development of Alzheimer’s disease (AD). We sought to identify the brain regions most vulnerable to BBBd during aging and examine their regional relationship with neuroimaging biomarkers of AD.MethodsWe studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify Ktransvalues, as a measure of BBBd, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)-PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBd than YA. In OA, Ktransvalues were compared based on sex, Aβ positivity status, and APOE4carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between Ktransand AD biomarkers.ResultsOA showed greater BBBd than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in Ktransvalues based on sex or Aβ positivity, but OA who were APOE4carriers had significantly higher Ktransvalues. There was no direct relationship between averaged Ktransand global Aβ pathology, but there was a trend for an Aβ status by tau interaction on Ktransin this region. SCCA showed increased Ktranswas associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between Ktransand FTP SUVR.DiscussionOur findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBd in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of Aβ.