Although amyloid-β plaques are one of the hallmarks of Alzheimer’s disease, scientists still don’t know what triggers the formation of the peptide clumps or what they do to surrounding brain tissue. A new technique that produces three-dimensional images of such plaques in mouse and human brains could help researchers start to answer those questions, say the method’s developers (Cell Rep. 2016, DOI: 10.1016/j.celrep.2016.06.060). To produce such images, Marc Flajolet of Rockefeller University and coworkers start by staining the amyloid plaques using either antibodies or small-molecule dyes. Then they treat the brain tissue with a series of organic solvents to remove lipids, making the tissue transparent. Finally, light-sheet microscopy allows the researchers to image the entire sample over a couple hours, by snapping photos of individual planes of the tissue as they go. Although plaques in mouse brains were fairly uniform in size and mostly spherical, human plaques appeared more varied, with some large, complex shapes. Flajolet now aims to investigate whether variations in plaque shape correspond to differences in disease progression in patients. Also, by staining blood vessels, other brain features, and various types of cells, the researchers hope to better understand the environment around plaques as they form.