{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:05:27Z","timestamp":1792073127525,"version":"4.4.0"},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>X\u2010linked adrenoleukodystrophy (X\u2010ALD) and metachromatic leukodystrophy (MLD) are two relatively common examples of hereditary demyelinating diseases caused by a dysfunction of peroxisomal or lysosomal lipid degradation. In both conditions, accumulation of nondegraded lipids leads to the destruction of cerebral white matter. Because of their high lipid content, oligodendrocytes are considered key to the pathophysiology of these leukodystrophies. However, the response to allogeneic stem cell transplantation points to the relevance of cells related to the hematopoietic lineage. In the present study, we aimed to better characterize the pathogenetic role of microglia in the above\u2010mentioned diseases. Applying recently established microglia markers to human autopsy cases of X\u2010ALD and MLD we were able to delineate distinct lesion stages in evolving demyelinating lesions. The immune\u2010phenotype of microglia was altered already early in lesion evolution, and microglia loss preceded full\u2010blown myelin degeneration both in X\u2010ALD and MLD. DNA fragmentation indicating phagocyte death was observed in areas showing microglia loss. The morphology and dynamics of phagocyte decay differed between the diseases and between lesion stages, hinting at distinct pathways of programmed cell death. In summary, the present study shows an early and severe damage to microglia in the pathogenesis of X\u2010ALD and MLD. This hints at a central pathophysiologic role of these cells in the diseases and provides evidence for an ongoing transfer of toxic substrates primarily enriched in myelinating cells to microglia.<\/jats:p>","DOI":"10.1002\/glia.23598","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:49:00Z","timestamp":1549943340000},"page":"1196-1209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Microglia damage precedes major myelin breakdown in X\u2010linked adrenoleukodystrophy and metachromatic leukodystrophy"],"prefix":"10.1002","volume":"67","author":[{"given":"Caroline G.","family":"Bergner","sequence":"first","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Wrzos","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mevlude","family":"T\u00fcrkmen","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"},{"name":"Department of Cardiology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Valizada","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Fitzner","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Hametner","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"},{"name":"Institute of Neurology, Medical University Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Section of Neuropathology, Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Pfeifenbring","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Stoltenburg\u2010Didinger","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology and Neurobiology, Charit\u00e9 University Medicine  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Br\u00fcck","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nessler","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1766-5458","authenticated-orcid":false,"given":"Christine","family":"Stadelmann","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001074"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525528113"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.02.034"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.12.005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00393.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.04.043"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-015-0520-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380514"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3599"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4183"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-008-8022-3"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1700554"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1739"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21391"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.00648.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000112164"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13989"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25085"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12399"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1997"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0120-6"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0090-8"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(98)00040-0"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13129"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.55.1.98"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000079050.91337.83"},{"key":"e_1_2_6_31_1","first-page":"1761","article-title":"Adrenoleukodystrophy: A scoring method for brain MR observations","volume":"15","author":"Loes D. J.","year":"1994","journal-title":"American Journal of Neuroradiology"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-28957-7_1"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70177-1"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.12703\/P6-13"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8670"},{"key":"e_1_2_6_36_1","first-page":"839","article-title":"X\u2010linked adrenoleukodystrophy: The role of contrast\u2010enhanced MR imaging in predicting disease progression","volume":"21","author":"Melhem E. R.","year":"2000","journal-title":"AJNR. American Journal of Neuroradiology"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23097"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.005"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws206"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-013101"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12163"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00342847"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3402"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3722"},{"key":"e_1_2_6_45_1","first-page":"306","article-title":"Detection of a monocyte\/macrophage differentiation antigen in routinely processed paraffin\u2010embedded tissues by monoclonal antibody Ki\u2010M1P","volume":"65","author":"Radzun H. J.","year":"1991","journal-title":"Laboratory Investigation; A Journal of Technical Methods and Pathology"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4325"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10293"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1975.00490510033001"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12595"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.055"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23458"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0619-8"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00009"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-009-9163-5"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-014-0142-6"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2016.04.003"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4547"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12551"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-27660-2"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt645"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy127"},{"key":"e_1_2_6_62_1","first-page":"109","article-title":"The genetic landscape of X\u2010linked adrenoleukodystrophy: Inheritance, mutations, modifier genes, and diagnosis","volume":"8","author":"Wiesinger C.","year":"2015","journal-title":"Application of Clinical Genetics"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0883-6"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021014-071649"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx113"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12583"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.23598","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.23598","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/glia.23598","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.23598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T19:03:34Z","timestamp":1693681414000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.23598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,11]]},"references-count":65,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/glia.23598"],"URL":"https:\/\/doi.org\/10.1002\/glia.23598","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,11]]},"assertion":[{"value":"2018-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}