Fig. 2: Dysmyelination and demyelination enhance amyloid plaque deposition in 5×FAD mice.
From: Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
a–d, LSM analysis of 6-month-old Cnp+/+;5xFAD and Cnp−/−;5xFAD mouse brains stained for Congo red. a, Representative LSM 2D single planes. Inlays show close-up images of the cortex and alveus. Arrowheads indicate small amyloid deposits in the alveus. b, 3D representation of hippocampal, isocortical and alveus plaques represented as coloured centroids. c, 3D cropped regions of interest (ROIs) of a representative brain rendered in maximum intensity modus. d, 3D quantification of plaque load in the indicated ROIs normalized to the controls. n = 8 for control, n = 7 for mutant. Ctrl, control; KO, knockout. e, Left, 2D immunostaining images of microglia (IBA1) and Aβ plaques with Me-04 (top two rows) or antibody-labelling (bottom row) in the alveus of cuprizone-treated 5×FAD mice (cuprizone 5×FAD) and control animals (5xFAD). Right, quantification of amyloid-positive deposits in the alveus. n = 4 for control, n = 5 for cuprizone treatment. f, Left, 2D immunostaining images of amyloid using antibody labelling (top two rows) or the β-sheet dye Me-04 (bottom row). EAE lesions are indicated by nuclei accumulations (DAPI or ToPro3 labelling) and marked by dashed lines. EAE control animals are shown to rule out nonspecific staining of lesion sites in EAE. Right, quantification of amyloid-positive deposits in the lesion environment. n = 5 for control, n = 5 for EAE treatment. For d–f, statistical analysis: two-sided, unpaired Student’s t-test (P values are indicated in the graphs). Bars represent the means, dots represent biological replicates/mice/n.
