Mesoscopic vascular alterations in Alzheimer's disease

Abstract

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.

Keywords: Alzheimer's disease; amyloid beta; cerebrovascular network; histopathology; human brain; optical coherence tomography; phosphorylated tau; vascular morphology.