Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-β plaques in Alzheimer’s disease models

Abstract

While numerous transgenic mouse strains have been produced to model the formation of amyloid-beta (A beta) plaques in the brain, efficient methods for whole-brain 3D analysis of A beta deposits have to be validated and standardized. Moreover, routine immunohistochemistry performed on brain slices precludes any shape analysis of A beta plaques, or require complex procedures for serial acquisition and reconstruction. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of A beta plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of A beta plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying priors-like properties of A beta aggregates in animal models of Alzheimer's disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue. (C) 2022 Optical Society of America under the terms of the OSA Open Access Publishing Agreement