Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis.
X-linked adrenoleukodystrophy
axonal injury
demyelination
multiple sclerosis
remyelination
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
26
05
2021
received:
23
02
2021
accepted:
28
05
2021
pubmed:
18
6
2021
medline:
12
3
2022
entrez:
17
6
2021
Statut:
ppublish
Résumé
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.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2362-2377Informations de copyright
© 2021 The Authors. GLIA published by Wiley Periodicals LLC.
Références
Barnett, M. H., & Prineas, J. W. (2004). Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion. Annals of Neurology, 55(4), 458-468. https://doi.org/10.1002/ana.20016
de Beer, M., Engelen, M., & van Geel, B. M. (2014). Frequent occurrence of cerebral demyelination in adrenomyeloneuropathy. Neurology, 83(24), 2227-2231. https://doi.org/10.1212/WNL.0000000000001074
Berger, J., Forss-Petter, S., & Eichler, F. S. (2014). Pathophysiology of X-linked adrenoleukodystrophy. Biochimie, 98, 135-142. https://doi.org/10.1016/j.biochi.2013.11.023
Berger, J., & Gärtner, J. (2006). X-linked adrenoleukodystrophy: Clinical, biochemical and pathogenetic aspects. Biochimica et Biophysica Acta, 1763(12), 1721-1732. https://doi.org/10.1016/j.bbamcr.2006.07.010
Bergner, C. G., van der Meer, F., Winkler, A., Wrzos, C., Türkmen, M., Valizada, E., … Stadelmann, C. (2019). Microglia damage precedes major myelin breakdown in X-linked adrenoleukodystrophy and metachromatic leukodystrophy. Glia, 67(6), 1196-1209. https://doi.org/10.1002/glia.23598
Bitsch, A., Schuchardt, J., Bunkowski, S., Kuhlmann, T., & Brück, W. (2000). Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain: A Journal of Neurology, 123(Pt 6), 1174-1183. https://doi.org/10.1093/brain/123.6.1174
Bjartmar, C., Kidd, G., Mörk, S., Rudick, R., & Trapp, B. D. (2000). Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Annals of Neurology, 48(6), 893-901.
Brück, W., Bitsch, A., Kolenda, H., Brück, Y., Stiefel, M., & Lassmann, H. (1997). Inflammatory central nervous system demyelination: Correlation of magnetic resonance imaging findings with lesion pathology. Annals of Neurology, 42(5), 783-793. https://doi.org/10.1002/ana.410420515
Charcot, J. M. (1868). Histologie de la sclerose en plaques, lecon faite a l hospice de la salpetriere. HACHETTE LIVRE: BNF. .
Coleman, M. (2005). Axon degeneration mechanisms: Commonality amid diversity. Nature Reviews. Neuroscience, 6(11), 889-898. https://doi.org/10.1038/nrn1788
Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A. D., Ujvári, K., Környei, Z., Tóth, K., Szabadits, E., Sperlágh, B., Baranyi, M., Csiba, L., Hortobágyi, T., Maglóczky, Z., … Dénes, Á. (2020). Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science (New York, N.Y.), 367(6477), 528-537. https://doi.org/10.1126/science.aax6752
Eichler, F. S., Barker, P. B., Cox, C., Edwin, D., Ulug, A. M., Moser, H. W., & Raymond, G. V. (2002). Proton MR spectroscopic imaging predicts lesion progression on MRI in X-linked adrenoleukodystrophy. Neurology, 58(6), 901-907. https://doi.org/10.1212/wnl.58.6.901
Eichler, F., Duncan, C., Musolino, P. L., Orchard, P. J., de Oliveira, S., Thrasher, A. J., Armant, M., Dansereau, C., Lund, T. C., Miller, W. P., Raymond, G. V., Sankar, R., Shah, A. J., Sevin, C., Gaspar, H. B., Gissen, P., Amartino, H., Bratkovic, D., Smith, N. J. C., … Williams, D. A. (2017). Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. The New England Journal of Medicine, 377(17), 1630-1638. https://doi.org/10.1056/NEJMoa1700554
Eichler, F. S., Itoh, R., Barker, P. B., Mori, S., Garrett, E. S., van Zijl, P. C. M., Moser, H. W., Raymond, G. V., & Melhem, E. R. (2002). Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: Initial experience. Radiology, 225(1), 245-252. https://doi.org/10.1148/radiol.2251011040
Eichler, F. S., Ren, J.-Q., Cossoy, M., Rietsch, A. M., Nagpal, S., Moser, A. B., Frosch, M. P., & Ransohoff, R. M. (2008). Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy? Annals of Neurology, 63(6), 729-742. https://doi.org/10.1002/ana.21391
Elmore, M. R. P., Najafi, A. R., Koike, M. A., Dagher, N. N., Spangenberg, E. E., Rice, R. A., Kitazawa, M., Matusow, B., Nguyen, H., West, B. L., & Green, K. N. (2014). Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron, 82(2), 380-397. https://doi.org/10.1016/j.neuron.2014.02.040
Engelen, M., Kemp, S., & Poll-The, B.-T. (2014). X-linked adrenoleukodystrophy: Pathogenesis and treatment. Current Neurology and Neuroscience Reports, 14(10), 486. https://doi.org/10.1007/s11910-014-0486-0
Fard, M. K., van der Meer, F., Sánchez, P., Cantuti-Castelvetri, L., Mandad, S., Jäkel, S., Fornasiero, E. F., Schmitt, S., Ehrlich, M., Starost, L., Kuhlmann, T., Sergiou, C., Schultz, V., Wrzos, C., Brück, W., Urlaub, H., Dimou, L., Stadelmann, C., & Simons, M. (2017). Bcas1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions. Science Translational Medicine, 9(419), eaam7816. https://doi.org/10.1126/scitranslmed.aam7816
Ferguson, B., Matyszak, M. K., Esiri, M. M., & Perry, V. H. (1997). Axonal damage in acute multiple sclerosis lesions. Brain: A Journal of Neurology, 120(Pt 3), 393-399. https://doi.org/10.1093/brain/120.3.393
Ferrer, I., Aubourg, P., & Pujol, A. (2010). General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain Pathology (Zurich, Switzerland), 20(4), 817-830. https://doi.org/10.1111/j.1750-3639.2010.00390.x
Fouquet, F., Zhou, J. M., Ralston, E., Murray, K., Troalen, F., Magal, E., Robain, O., Dubois-Dalcq, M., & Aubourg, P. (1997). Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system. Neurobiology of Disease, 3(4), 271-285. https://doi.org/10.1006/nbdi.1997.0127
Fourcade, S., Ferrer, I., & Pujol, A. (2015). Oxidative stress, mitochondrial and proteostasis malfunction in adrenoleukodystrophy: A paradigm for axonal degeneration. Free Radical Biology & Medicine, 88, 18-29. https://doi.org/10.1016/j.freeradbiomed.2015.05.041
Frischer, J. M., Bramow, S., Dal-Bianco, A., Lucchinetti, C. F., Rauschka, H., Schmidbauer, M., Laursen, H., Sorensen, P. S., & Lassmann, H. (2009). The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain: A Journal of Neurology, 132(5), 1175-1189. https://doi.org/10.1093/brain/awp070
Frischer, J. M., Weigand, S. D., Guo, Y., Kale, N., Parisi, J. E., Pirko, I., Mandrekar, J., Bramow, S., Metz, I., Brück, W., Lassmann, H., & Lucchinetti, C. F. (2015). Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Annals of Neurology, 78(5), 710-721. https://doi.org/10.1002/ana.24497
Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A. S., Edgar, J., Brinkmann, B. G., Kassmann, C. M., Tzvetanova, I. D., Möbius, W., Diaz, F., Meijer, D., Suter, U., Hamprecht, B., Sereda, M. W., Moraes, C. T., Frahm, J., Goebbels, S., & Nave, K.-A. (2012). Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature, 485(7399), 517-521. https://doi.org/10.1038/nature11007
Gelfand, J. M., Greenfield, A. L., Barkovich, M., Mendelsohn, B. A., van Haren, K., Hess, C. P., & Mannis, G. N. (2020). Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia. Brain: A Journal of Neurology, 143(2), 503-511. https://doi.org/10.1093/brain/awz390
Gong, Y., Sasidharan, N., Laheji, F., Frosch, M., Musolino, P., Tanzi, R., Kim, D. Y., Biffi, A., el Khoury, J., & Eichler, F. (2017). Microglial dysfunction as a key pathological change in adrenomyeloneuropathy. Annals of Neurology, 82(5), 813-827. https://doi.org/10.1002/ana.25085
Görtz, A. L., Peferoen, L. A. N., Gerritsen, W. H., van Noort, J. M., Bugiani, M., & Amor, S. (2018). Heat shock protein expression in cerebral X-linked adrenoleukodystrophy reveals astrocyte stress prior to myelin loss. Neuropathology and Applied Neurobiology, 44(4), 363-376. https://doi.org/10.1111/nan.12399
Höftberger, R., Kunze, M., Weinhofer, I., Aboul-Enein, F., Voigtländer, T., Oezen, I., … Berger, J. (2007). Distribution and cellular localization of adrenoleukodystrophy protein in human tissues: Implications for X-linked adrenoleukodystrophy. Neurobiology of Disease, 28(2), 165-174. https://doi.org/10.1016/j.nbd.2007.07.007
Horvath, G. A., Eichler, F., Poskitt, K., & Stockler-Ipsiroglu, S. (2012). Failure of repeated cyclophosphamide pulse therapy in childhood cerebral X-linked adrenoleukodystrophy. Neuropediatrics, 43(1), 48-52. https://doi.org/10.1055/s-0032-1307455
Kemp, S., Pujol, A., Waterham, H. R., van Geel, B. M., Boehm, C. D., Raymond, G. V., … Moser, H. W. (2001). Abcd1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations. Human Mutation, 18(6), 499-515. https://doi.org/10.1002/humu.1227
Konno, T., Kasanuki, K., Ikeuchi, T., Dickson, D. W., & Wszolek, Z. K. (2018). Csf1r-related leukoencephalopathy: A major player in primary microgliopathies. Neurology, 91(24), 1092-1104. https://doi.org/10.1212/WNL.0000000000006642
Koo, E. H., Sisodia, S. S., Archer, D. R., Martin, L. J., Weidemann, A., Beyreuther, K., Fischer, P., Masters, C. L., & Price, D. L. (1990). Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proceedings of the National Academy of Sciences of the United States of America, 87(4), 1561-1565. https://doi.org/10.1073/pnas.87.4.1561
Kuhlmann, T., Lingfeld, G., Bitsch, A., Schuchardt, J., & Brück, W. (2002). Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain: A Journal of Neurology, 125(Pt 10), 2202-2212. https://doi.org/10.1093/brain/awf235
Kuhlmann, T., Ludwin, S., Prat, A., Antel, J., Brück, W., & Lassmann, H. (2017). An updated histological classification system for multiple sclerosis lesions. Acta Neuropathologica, 133(1), 13-24. https://doi.org/10.1007/s00401-016-1653-y
Lee, Y., Morrison, B. M., Li, Y., Lengacher, S., Farah, M. H., Hoffman, P. N., Liu, Y., Tsingalia, A., Jin, L., Zhang, P. W., Pellerin, L., Magistretti, P. J., & Rothstein, J. D. (2012). Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature, 487(7408), 443-448. https://doi.org/10.1038/nature11314
Liberato, A. P., Mallack, E. J., Aziz-Bose, R., Hayden, D., Lauer, A., Caruso, P. A., Musolino, P. L., & Eichler, F. S. (2019). Mri brain lesions in asymptomatic boys with X-linked adrenoleukodystrophy. Neurology, 92(15), e1698-e1708. https://doi.org/10.1212/WNL.0000000000007294
Mahad, D. H., Trapp, B. D., & Lassmann, H. (2015). Pathological mechanisms in progressive multiple sclerosis. The Lancet Neurology, 14(2), 183-193. https://doi.org/10.1016/S1474-4422(14)70256-X
Mahmood, A., Raymond, G. V., Dubey, P., Peters, C., & Moser, H. W. (2007). Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: A comparison study. The Lancet Neurology, 6(8), 687-692. https://doi.org/10.1016/S1474-4422(07)70177-1
Mallack, E. J., van de Stadt, S., Caruso, P. A., Musolino, P. L., Sadjadi, R., Engelen, M., & Eichler, F. S. (2020). Clinical and radiographic course of arrested cerebral adrenoleukodystrophy. Neurology, 94(24), e2499-e2507. https://doi.org/10.1212/WNL.0000000000009626
Mochel, F., Delorme, C., Czernecki, V., Froger, J., Cormier, F., Ellie, E., Fegueux, N., Lehéricy, S., Lumbroso, S., Schiffmann, R., Aubourg, P., Roze, E., Labauge, P., & Nguyen, S. (2019). Haematopoietic stem cell transplantation in CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. Journal of Neurology, Neurosurgery, and Psychiatry, 90(12), 1375-1376. https://doi.org/10.1136/jnnp-2019-320701
Moser, H. W., Naidu, S., Kumar, A. J., & Rosenbaum, A. E. (1987). The adrenoleukodystrophies. Critical Reviews in Neurobiology, 3(1), 29-88.
Mosser, J., Douar, A. M., Sarde, C. O., Kioschis, P., Feil, R., Moser, H., Poustka, A. M., Mandel, J. L., & Aubourg, P. (1993). Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature, 361(6414), 726-730. https://doi.org/10.1038/361726a0
Musolino, P. L., Gong, Y., Snyder, J. M. T., Jimenez, S., Lok, J., Lo, E. H., Moser, A. B., Grabowski, E. F., Frosch, M. P., & Eichler, F. S. (2015). Brain endothelial dysfunction in cerebral adrenoleukodystrophy. Brain: A Journal of Neurology, 138(Pt 11), 3206-3220. https://doi.org/10.1093/brain/awv250
Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., & Bennett, J. T. (2019). Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia. American Journal of Human Genetics, 104(5), 936-947. https://doi.org/10.1016/j.ajhg.2019.03.010
Oyanagi, K., Kinoshita, M., Suzuki-Kouyama, E., Inoue, T., Nakahara, A., Tokiwai, M., … Ikeda, S.-I. (2017). Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets. Brain Pathology (Zurich, Switzerland), 27(6), 748-769. https://doi.org/10.1111/bpa.12443
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., Ragozzino, D., & Gross, C. T. (2011). Synaptic pruning by microglia is necessary for normal brain development. Science (New York, N.Y.), 333(6048), 1456-1458. https://doi.org/10.1126/science.1202529
Patrikios, P., Stadelmann, C., Kutzelnigg, A., Rauschka, H., Schmidbauer, M., Laursen, H., Sorensen, P. S., Bruck, W., Lucchinetti, C., & Lassmann, H. (2006). Remyelination is extensive in a subset of multiple sclerosis patients. Brain: A Journal of Neurology, 129(Pt 12), 3165-3172. https://doi.org/10.1093/brain/awl217
Périer, O., & Grégoire, A. (1965). Electron microscopic features of multiple sclerosis lesions. Brain: A Journal of Neurology, 88(5), 937-952. https://doi.org/10.1093/brain/88.5.937
Powers, J. M., Liu, Y., Moser, A. B., & Moser, H. W. (1992). The inflammatory myelinopathy of adreno-leukodystrophy: Cells, effector molecules, and pathogenetic implications. Journal of Neuropathology and Experimental Neurology, 51(6), 630-643. https://doi.org/10.1097/00005072-199211000-00007
Powers, J. M., & Schaumburg, H. H. (1981). The testis in adreno-leukodystrophy. The American Journal of Pathology, 102(1), 90-98.
Powers, J. M., Moser, H. W., Moser, A. B., & Schaumburg, H. H. (1982). Fetal adrenoleukodystrophy: The significance of pathologic lesions in adrenal gland and testis. Human Pathology, 13(11), 1013-1019. https://doi.org/10.1016/S0046-8177(82)80093-2
Prinz, M., Jung, S., & Priller, J. (2019). Microglia biology: One century of evolving concepts. Cell, 179(2), 292-311. https://doi.org/10.1016/j.cell.2019.08.053
Pujol, A., Ferrer, I., Camps, C., Metzger, E., Hindelang, C., Callizot, N., Ruiz, M., Pàmpols, T., Giròs, M., & Mandel, J. L. (2004). Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: A therapeutic target for X-adrenoleukodystrophy. Human Molecular Genetics, 13(23), 2997-3006. https://doi.org/10.1093/hmg/ddh323
Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M., & Mandel, J. L. (2002). Late onset neurological phenotype of the X-ALD gene inactivation in mice: A mouse model for adrenomyeloneuropathy. Human Molecular Genetics, 11(5), 499-505. https://doi.org/10.1093/hmg/11.5.499
Radzun, H. J., Hansmann, M. L., Heidebrecht, H. J., Bödewadt-Radzun, S., Wacker, H. H., Kreipe, H., Lumbeck, H., Hernandez, C., Kuhn, C., & Parwaresch, M. R. (1991). Detection of a monocyte/macrophage differentiation antigen in routinely processed paraffin-embedded tissues by monoclonal antibody Ki-M1P. Laboratory Investigation: A Journal of Technical Methods and Pathology, 65(3), 306-315.
Raymond, G. V., Aubourg, P., Paker, A., Escolar, M., Fischer, A., Blanche, S., Baruchel, A., Dalle, J. H., Michel, G., Prasad, V., Miller, W., Paadre, S., Balser, J., Kurtzberg, J., Nascene, D. R., Orchard, P. J., & Lund, T. (2019). Survival and functional outcomes in boys with cerebral adrenoleukodystrophy with and without hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation, 25(3), 538-548. https://doi.org/10.1016/j.bbmt.2018.09.036
Rojo, R., Raper, A., Ozdemir, D. D., Lefevre, L., Grabert, K., Wollscheid-Lengeling, E., Bradford, B., Caruso, M., Gazova, I., Sánchez, A., Lisowski, Z. M., Alves, J., Molina-Gonzalez, I., Davtyan, H., Lodge, R. J., Glover, J. D., Wallace, R., Munro, D. A. D., David, E., … Pridans, C. (2019). Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nature Communications, 10(1), 3215. https://doi.org/10.1038/s41467-019-11053-8
Rosewich, H., Nessler, S., Brück, W., & Gärtner, J. (2019). B cell depletion can be effective in multiple sclerosis but failed in a patient with advanced childhood cerebral X-linked adrenoleukodystrophy. Therapeutic Advances in Neurological Disorders, 12. https://doi.org/10.1177/1756286419868133
Schaumburg, H. H., Powers, J. M., Raine, C. S., Suzuki, K., & Richardson, E. P. (1975). Adrenoleukodystrophy. A clinical and pathological study of 17 cases. Archives of Neurology, 32(9), 577-591. https://doi.org/10.1001/archneur.1975.00490510033001
Schlüter, A., Sandoval, J., Fourcade, S., Díaz-Lagares, A., Ruiz, M., Casaccia, P., Esteller, M., & Pujol, A. (2018). Epigenomic signature of adrenoleukodystrophy predicts compromised oligodendrocyte differentiation. Brain Pathology (Zurich, Switzerland), 28(6), 902-919. https://doi.org/10.1111/bpa.12595
Siffrin, V., Radbruch, H., Glumm, R., Niesner, R., Paterka, M., Herz, J., Leuenberger, T., Lehmann, S. M., Luenstedt, S., Rinnenthal, J. L., Laube, G., Luche, H., Lehnardt, S., Fehling, H. J., Griesbeck, O., & Zipp, F. (2010). In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity, 33(3), 424-436. https://doi.org/10.1016/j.immuni.2010.08.018
Spencer, P. S., & Schaumburg, H. H. (1977a). Ultrastructural studies of the dying-back process. III. The evolution of experimental peripheral giant axonal degeneration. Journal of Neuropathology and Experimental Neurology, 36(2), 276-299. https://doi.org/10.1097/00005072-197703000-00005
Spencer, P. S., & Schaumburg, H. H. (1977b). Ultrastructural studies of the dying-back process. IV. Differential vulnerability of PNS and CNS fibers in experimental central-peripheral distal axonopathies. Journal of Neuropathology and Experimental Neurology, 36(2), 300-320. https://doi.org/10.1097/00005072-197703000-00006
Stadelmann, C., Timmler, S., Barrantes-Freer, A., & Simons, M. (2019). Myelin in the central nervous system: Structure, function, and pathology. Physiological Reviews, 99(3), 1381-1431. https://doi.org/10.1152/physrev.00031.2018
Stys, P. K. (2005). General mechanisms of axonal damage and its prevention. Journal of the Neurological Sciences, 233(1-2), 3-13. https://doi.org/10.1016/j.jns.2005.03.031
Theda, C., Moser, A. B., Powers, J. M., & Moser, H. W. (1992). Phospholipids in X-linked adrenoleukodystrophy white matter: Fatty acid abnormalities before the onset of demyelination. Journal of the Neurological Sciences, 110(1-2), 195-204. https://doi.org/10.1016/0022-510X(92)90028-J
Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., Mörk, S., & Bö, L. (1998). Axonal transection in the lesions of multiple sclerosis. The New England Journal of Medicine, 338(5), 278-285. https://doi.org/10.1056/NEJM199801293380502
Trapp, B. D., Vignos, M., Dudman, J., Chang, A., Fisher, E., Staugaitis, S. M., Battapady, H., Mork, S., Ontaneda, D., Jones, S. E., Fox, R. J., Chen, J., Nakamura, K., & Rudick, R. A. (2018). Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: A retrospective study. The Lancet Neurology, 17(10), 870-884. https://doi.org/10.1016/S1474-4422(18)30245-X
Weber, F. D., Wiesinger, C., Forss-Petter, S., Regelsberger, G., Einwich, A., Weber, W. H. A., Kohler, W., Stockinger, H., & Berger, J. (2014). X-linked adrenoleukodystrophy: Very long-chain fatty acid metabolism is severely impaired in monocytes but not in lymphocytes. Human Molecular Genetics, 23(10), 2542-2550. https://doi.org/10.1093/hmg/ddt645
Weinhofer, I., Zierfuss, B., Hametner, S., Wagner, M., Popitsch, N., Machacek, C., … Berger, J. (2018). Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain: A Journal of Neurology, 141(8), 2329-2342. https://doi.org/10.1093/brain/awy127
Yang, J., Weimer, R. M., Kallop, D., Olsen, O., Wu, Z., Renier, N., Uryu, K., & Tessier-Lavigne, M. (2013). Regulation of axon degeneration after injury and in development by the endogenous calpain inhibitor calpastatin. Neuron, 80(5), 1175-1189. https://doi.org/10.1016/j.neuron.2013.08.034