A NEUROINFLAMMATORY BIOMARKER SIGNATURE OF BLOOD-BRAIN BARRIER IMPAIRMENT IN OLDER ADULTS

Abstract

BBB damage is prevalent at post mortem brain tissue examination in all dementias, including Alzheimer’s disease (AD) cases versus age-matched controls. The CSF-to-serum albumin ratio, a clinical measure of BBB function, is associated with AD progression independent of age and vascular risk factors. If BBB dysfunction is significant to AD risk and progression then factors that modulate it are of keen interest. We hypothesized that biomarkers of neuroinflammation in CSF and serum would identify subjects with BBB impairment. CSF and serum were collected from 118 older adults to examine the cross-sectional relationship between a panel of “neuroinflammatory” biomarkers and BBB impairment defined a priori as a CSF-to-serum albumin ratio ≥ 9.0. LASSO regression selected the biomarkers that best classified subjects with BBB impairment. Area under the receiver operating characteristics were generated to assess diagnostic accuracy. Mean age was 70 years, 64% were female and the mean MMSE was 27. BBB impairment was more prevalent in subjects with CDR = 0.5 compared to subjects with CDR = 0. One predictive model including CSF inflammatory biomarkers provided a diagnostic accuracy for subjects with BBB impairment at 92.3% (AUC = 0.95 [0.88-0.99]). Another model to predict BBB impairment using serum inflammatory markers provided a diagnostic accuracy of 92.2% (AUC = 0.93 [0.87-0.98]). BBB impairment is functionally relevant in older community-living adults. CSF and serum neuroinflammatory biomarkers can effectively identify older adults with BBB impairment. These findings suggest that neuroinflammation plays a role in BBB breakdown seen in aging and dementia.