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

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 are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of A{beta} plaques. 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 prion-like properties of A{beta} aggregates in animal models of Alzheimers 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. HighlightsO_LIX-ray phase-contrast tomography (XPCT) enables whole brain detection of A{beta} plaques C_LIO_LIMorphometric parameters of A{beta} plaques may be readily retrieved from XPCT data C_LIO_LINew shape parameters were successfully extracted from three Alzheimers disease models C_LIO_LIA Fiji-based "biologist-friendly" analysis workflow is proposed and shared C_LIO_LIXPCT is a powerful virtual histology tool that requires minimal sample preparation C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/436908v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@7c3167org.highwire.dtl.DTLVardef@18f689eorg.highwire.dtl.DTLVardef@1d9c72org.highwire.dtl.DTLVardef@a027a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG