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

Brain Behav. 2022 Nov 21:e2806. doi: 10.1002/brb3.2806. Online ahead of print.

ABSTRACT

INTRODUCTION: Studies 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 (APOEε4) genotype, the biggest risk factor for late onset, non-familial AD (LOAD) with APOEε3 carriers, the population norm.

METHODS: Forty-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.

RESULTS: Non-significant, but subtle differences in blood-brain barrier permeability were identified between healthy mid-age APOEε4 and APOEε3 carriers, matched on age, education, and gender.

DISCUSSION: This study demonstrated a tendency toward BBB permeability in APOEε4 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 ε4 carrier BBB that may help identify at-risk populations and facilitate the development of early interventions to change the trajectory of decline.

PMID:36408825 | DOI:10.1002/brb3.2806

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