Mesoscopic vascular alterations in Alzheimer's disease.

INTRODUCTION

Cerebrovascular alterations are associated with the pathology of Alzheimer's disease (AD). Yet, the role of these alterations is not fully understood, partly due to a paucity of data from mesoscopic vasculature (24-240 µm diameter).

METHODS

We used label-free, serial-sectioning optical coherence tomography to reconstruct mesoscopic cerebrovasculature of the dorsolateral prefrontal cortex (DLPFC) samples from AD and control subjects. We quantified three-dimensional alterations to the vascular networks and measured the correlations between vascular alterations and deposits of amyloid β protein (Aβ) and phosphorylated tau protein (p-tau).

RESULTS

The AD group had significantly reduced volume fraction, vessel length density, and branch density. There were negative trends between a subset of the vascular metrics and the density of Aβ and p-tau.

DISCUSSION: AD samples in DLPFC present with significant mesoscopic cerebrovasculature alterations. This insight helps close the knowledge gap between micro- and macroscopic cerebrovascular pathologies.

HIGHLIGHTS: Volumetric imaging of mesoscopic cerebrovasculature with serial-sectioning optical coherence tomography (OCT). Vascular metrics: volume fraction, length density, branch density, and tortuosity. Human ex vivo samples from dorsolateral prefrontal cortex (Alxzheimer's disease [AD] and controls). Compared to controls, AD had reduced vascularity. Serial-sectioning OCT provides novel insights into mesoscopic cerebrovasculature.