Related Experiment Video
Updated: Aug 22, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
APOE ε4-related blood-brain barrier disruption and APOE ε4-independent microstructural abnormalities in white matter
Yuki Oi1, Qian Shen1, Seraphina K Solders1
1Department of Neurosciences University of California, San Diego La Jolla California USA.
Introduction:
While the apolipoprotein E (APOE) ε4 allele promotes blood-brain barrier (BBB) permeability and microstructural disruption, its specific contribution to white matter hyperintensity (WMH) pathological heterogeneity remains unknown.
Methods:
We measured BBB permeability (K trans) in 31 and microstructure in 59 cognitively normal older adults with WMHs and normal-appearing white matter (NAWM) using dynamic contrast-enhanced magnetic resonance imaging and restriction spectrum imaging (RSI). Linear mixed-effects models (LMMs) examined differences between WMHs and NAWM by APOE ε4 status.
Results:
In APOE ε4 carriers, K trans was elevated and restricted isotropic diffusion (RI) was reduced within WMHs compared to NAWM. This effect was absent in non-carriers. In contrast, reduced restricted directional diffusion and elevated isotropic free water within WMHs was observed in both genotypes. K trans did not correlate with brain microstructure.
Discussion:
Our data suggest that WMHs comprise both APOE ε4-related and APOE ε4-independent pathological components. These findings implicate neurovascular and non-vascular mechanisms through which APOE ε4 may contribute to WMH pathological heterogeneity.
Related Concept Videos
Alzheimer Disease l: Introduction
Cerebral Edema ll: Pathophysiology
Alzheimer Disease ll: Pathophysiology
Cerebral Edema l: Introduction

