APOE ε4‐related blood–brain barrier disruption and APOE ε4‐independent microstructural abnormalities in white matter hyperintensities
Yuki Oi, Qian Shen, Seraphina K. Solders, Charlotte S. Rivera, McKenna E. Williams, Emilie T. ReasAbstract
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.