Extended Data Fig. 1: Cortical myelin levels and gliosis in AD patients, aged wildtype mice and myelin mutants.
From: Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Continuation of Fig. 1. (a) Merge and single channel images showing microglia (stained with Iba1) and myelin levels (stained with PLP/CNP) as shown in Fig. 1. (b) Quantification of microgliosis and myelin levels in AD patients and non-AD controls as percentage area covered in the cortical areas examined. Bars represent means; dots represent individual patients/biological replicate/n (n = 3 per group). Statistical analysis: two-sided, unpaired Student’s t-test (p-value is given in graph). (c) Experimental setup to study the effect of myelin dysfunction on amyloid plaque load in AD mouse models. Models of genetic myelin dysfunction, acute demyelination and genetic amyelination were combined with the 5xFAD and AppNLGF model of AD and effects on amyloid deposition were investigated in toto by tissue clearing and light sheet microscopy (LSM). (d) Myelin defects drive a premature ageing phenotype in mice. Panels show microscopic images of immunolabellings against MBP (Myelin), GFAP (Astrogliosis), and Iba1 (Microgliosis) in 6-month-old wildtype, 24-month-old wildtype, 6-month-old myelin mutant (Cnp−/− and Plp−/y) mice. Regions of interest (ROI) analysed are indicated on the left. Dashed lines in the upper panel mark the pial surface above the cortex (CTX). Dashed lines in lower panels outline the corpus callosum (CC). (e) Heatmap representation of the quantification of myelin pathology and gliosis immunostainings as shown in (c) in myelin mutants (Cnp−/− and Plp−/y) and wildtype mice at 3-months (3m), 6-months (6m) and 24-months (24m). The percentage area covered was quantified in the indicated ROIs and is presented as fold-change (FC) with respect to the 3-month-old data set. Each heatmap tile represents a single animal/biological replicate/n (n = 3 per group) and is colour-coded according to the row minimum-maximum lookup table shown below. Statistical analysis and raw values are given in Supplementary Fig. 2.
