Fluoro-Jade is a fluorescein-derived fluorochrome which specifically binds to damaged neurons. Due to this characteristic, it is commonly used for the histochemical detection and quantification of neurodegeneration in mounted brain sections. Here, we describe an alternative and simpler histochemistry protocol based on the use of free-floating brain sections. For this purpose, we have used brain slices from wild-type and 5xFAD mice as well as from mice that received an intracerebral injection of oligomeric amyloid beta peptides. We observed that our histochemistry staining procedure allows for a well-defined labeling of degenerating neurons providing a better signal-to-noise ratio staining than the commonly used one. In addition, our modified protocol demonstrates the ability of Fluoro-Jade C to also fluorescently label amyloid beta plaques.