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. 2023 Jun 20;11:100. doi: 10.1186/s40478-023-01598-7

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Reduced myelinated axon density in NAWM, while total myelinated axon area and g-ratio are unaffected. A Representative scanning transmission electron microscopic images (STEM) images of post-mortem control white matter (CGM) of control donors (from donor CM 1) normal appearing white matter (NAWM) of donors with progressive MS (from donor NAM 6). Top: overview images. Bottom: detailed images from boxed regions in top images. n = nucleus, bv = blood vessel, m = mitochondria. Scale bars represent 5 µm (top images) or 0.5 µm (bottom images). B, C Violin plots depict the number of myelinated axons (B) and their total area (C, red) in an area of 20 × 20 µm. D Histogram with kernel density estimation of the axon radius (r). E Violin plot depicts the distribution of g-ratio (r/R). Datapoints represent mean per donor (B, C, E ● = female (SPMS), ▲ = male (SPMS), △ = male (PPMS), color-coded, see Table 1) and boxplots show the median and inter quartile range (IQR). F Scatter plot showing the g-ratio versus axon radius (log-linear fit). Number of control donors (CWM) is 4, number of donors with progressive MS (NAWM) is 7, 200 myelinated axons per donor (D–F), and 25 areas of 20 × 20 µm (B, C) were analysed. Statistics were performed using an unpaired Student’s t test (D), or a linear mixed model (B, C, E) (*p < 0.05; **p < 0.01; ***p < 0.001)