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  Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis

Bergner, C. G., Genc, N., Hametner, S., Franz, J., van der Meer, F., Mitkovski, M., et al. (2021). Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis. Glia, 69(10), 2362-2377. doi:10.1002/glia.24042.

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Bergner, Caroline G., Author
Genc, Nafiye, Author
Hametner, Simon, Author
Franz, Jonas1, Author
van der Meer, Franziska, Author
Mitkovski, Miso2, Author           
Weber, Martin S., Author
Stoltenburg-Didinger, Gisela, Author
Kühl, Jörn-Sven, Author
Köhler, Wolfgang, Author
Brück, Wolfgang, Author
Gärtner, Jutta, Author
Stadelmann, Christine, Author
1Max Planck Institute of Experimental Medicine, Max Planck Society, Hermann-Rein-Str. 3, 37075 Göttingen, DE, ou_2173648              
2Light microscopy facility, Wiss. Servicegruppen, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173672              


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 Abstract: Cerebral disease manifestation occurs in about two thirds of males with X-linked adrenoleukodystrophy (CALD) and is fatally progressive if left untreated. Early histopathologic studies categorized CALD as an inflammatory demyelinating disease, which led to repeated comparisons to multiple sclerosis (MS). The aim of this study was to revisit the relationship between axonal damage and myelin loss in CALD. We applied novel immunohistochemical tools to investigate axonal damage, myelin loss and myelin repair in autopsy brain tissue of eight CALD and 25 MS patients. We found extensive and severe acute axonal damage in CALD already in prelesional areas defined by microglia loss and relative myelin preservation. In contrast to MS, we did not observe selective phagocytosis of myelin, but a concomitant decay of the entire axon-myelin unit in all CALD lesion stages. Using a novel marker protein for actively remyelinating oligodendrocytes, breast carcinoma-amplified sequence (BCAS) 1, we show that repair pathways are activated in oligodendrocytes in CALD. Regenerating cells, however, were affected by the ongoing disease process. We provide evidence that—in contrast to MS—selective myelin phagocytosis is not characteristic of CALD. On the contrary, our data indicate that acute axonal injury and permanent axonal loss are thus far underestimated features of the disease that must come into focus in our search for biomarkers and novel therapeutic approaches.


Language(s): eng - English
 Dates: 2021-06-172021-10
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/glia.24042
 Degree: -



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Project name : The present study was supported by the European Leukodystrophies Association (ELA) to Christine Stadelmann, the Deutsche Forschungsgemeinschaft (DFG) transregional collaborative research center (CRC) 274 “Checkpoints of CNS recovery” (Jutta Gärtner, Wolfgang Brück, and Christine Stadelmann), STA 1389/5-1, GA 354/14-1, the DFG under Germany's Excellence Strategy (EXC 2067/1; Jutta Gärtner), the Gemeinnützige Hertie Foundation, the Deutsche Multiple Sklerose Gesellschaft (DMSG, Christine Stadelmann), and the National MS Society (USA, Christine Stadelmann). Caroline G. Bergner was supported as fellow of the Forschungskolleg TRANSMED at the University Medical Center Göttingen by the Ministry of Science and Lower Saxony. Nafiye Genc was supported by the Gemeinnützige Hertie Stiftung as a fellow in the medMS program. Franziska van der Meer held a Dorothea Schlözer postdoctoral stipend of the University Medical Center Göttingen. Jonas Franz is supported by the clinician scientist program of the CRC 274. Open Access funding enabled and organized by Projekt DEAL.
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Source 1

Title: Glia
  Other : Glia
Source Genre: Journal
Publ. Info: New York, N.Y. : Wiley-Liss, Inc.
Pages: - Volume / Issue: 69 (10) Sequence Number: - Start / End Page: 2362 - 2377 Identifier: ISSN: 0894-1491
CoNE: https://pure.mpg.de/cone/journals/resource/954925558509