Fig. 1

Intra- and inter-size variations of AxDs over time. (a-c), Maximum projection (40 optical sections, z-step = 1 μm) of a stack of images taken with a two-photon microscope in the somatosensory cortex of a dE9 mouse at three different time points. Small AxDs (yellow and red arrows, dys 6 and 7, respectively) in GFP-expressing axons (green) are present around an Aβ plaque stained with Methoxy-X04 (blue). (d-i), Maximum projection (32 optical sections, z-step = 1 μm) of a stack of images taken with the two-photon microscope in the somatosensory cortex of the APP-PS1 mouse at six different time points. A large AxD (brackets in e-h; dys 4) in a GFP-expressing axon (green; arrowheads) is present around an Aβ plaque stained with Methoxy-X04 (blue). This plaque was observed growing in size from its birth (d) to maturation (i). There is a degeneration of the distal part of the axon and the AxD remains at the edge of the proximal part of the axon (h). On the final day of imaging, the whole axon had disappeared (i). AxDs in panels a-c do not show strong variations in size and shape over time as compared to the AxD in panels d-i, and numerous axons and dendritic processes do not become dystrophic. There is an axon segment that does not become dystrophic and disappears (white arrow). (j-m), 3D reconstructions of the AxD showed in images e-h, respectively, using Imaris software. The dystrophic segment of the axon is shown in red and this is the portion of the axon that was used to calculate the AxD volume (Fig. 3b). The days shown refer to the number of days after day 0 (when imaging began). Purple arrows in g-i point out a re-growing axon that is also shown in greater detail in Fig. 5. Scale bar (in m): 19.5 μm in a-m