Evidence of emerging BBB changes in mid-age apolipoprotein E epsilon-4 carriers

IntroductionStudies have recognized that the loss of the blood-brain barrier (BBB) integrity is a major structural biomarker where neurodegenerative disease potentially begins. Using a combination of high-quality neuroimaging techniques, we investigated potential subtle differences in BBB permeability in mid-age healthy people, comparing carriers of the apolipoprotein E epsilon-4 (APOE epsilon 4) genotype, the biggest risk factor for late onset, non-familial AD (LOAD) with APOE epsilon 3 carriers, the population norm. MethodsForty-one cognitively healthy mid-age participants (42-59) were genotyped and pseudo-randomly selected to participate in the study by a third party. Blind to genotype, all participants had a structural brain scan acquisition including gadolinium-based dynamic contrast-enhanced magnetic resonance imaging acquired using a T1-weighted 3D vibe sequence. A B1 map and T1 map were acquired as part of the multi-parametric mapping acquisition. ResultsNon-significant, but subtle differences in blood-brain barrier permeability were identified between healthy mid-age APOE epsilon 4 and APOE epsilon 3 carriers, matched on age, education, and gender. DiscussionThis study demonstrated a tendency toward BBB permeability in APOE epsilon 4 participants emerging from mid-age, with quantitative differences observable on a number of the measures. While the differences did not reach a statistical significance, the results from this study hint at early changes in epsilon 4 carrier BBB that may help identify at-risk populations and facilitate the development of early interventions to change the trajectory of decline.

Automated summary

This study investigated potential subtle differences in blood-brain barrier permeability in carriers of the APOE epsilon-4 genotype compared to carriers of the APOE epsilon-3 genotype. Although the differences were not statistically significant, they suggest early changes in BBB permeability in APOE epsilon-4 carriers, which may help identify at-risk populations and facilitate early interventions to change the trajectory of neurodegenerative decline.