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Cited by 20Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchHereditary Neurological Disorders

The pathology of X-linked adrenoleukodystrophy: Tissue specific changes as a clue to pathophysiology

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Yska, Hemmo A.F., Engelen, Marc, Bugiani, Marianna·2024·Orphanet Journal of Rare Diseases
DOI 10.1186/s13023-024-03105-0PMC PMC10976706
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Abstract

Although the pathology of X-linked adrenoleukodystrophy (ALD) is well described, it represents the end-stage of neurodegeneration. It is still unclear what cell types are initially involved and what their role is in the disease process. Revisiting the seminal post-mortem studies from the 1970s can generate new hypotheses on pathophysiology. This review describes (histo)pathological changes of the brain and spinal cord in ALD. It aims at integrating older works with current insights and at providing an overarching theory on the pathophysiology of ALD. The data point to an important role for axons and glia in the pathology of both the myelopathy and leukodystrophy of ALD. In-depth pathological analyses with new techniques could help further unravel the sequence of events behind the pathology of ALD.

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  • In many neurodegenerative diseases, including AMN, axonal pathology precedes cell body loss in the form of dying back axonopathy.

    “In many neurodegenerative diseases, including AMN [49,89,181,187,288,294,295,296,297], axonal pathology precedes cell body loss in the form of “dying back axonopathy”, in which axons gradually degenerate toward the cell body [298,299].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [295]

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References 88 · Cited by 20

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Authors
Yska, H. A. F., Engelen, M., & Bugiani, M.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Amsterdam Neuroscience (NL)
Corresponding author
Yska, Hemmo A.F.
ORCID
Venue
Orphanet Journal of Rare Diseases
Publisher
Springer Science and Business Media LLC
Published
2024-03-28
Volume
19
Issue
1
Pages
138-138
ISSN
1750-1172 (ISSN-L)
DOI
10.1186/s13023-024-03105-0
PMC
PMC10976706
OpenAlex
W4393262551
Cited by
20
References
88
Citations by year
2026: 6 · 2025: 10 · 2024: 3
FWCI
1.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (016.196.310)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
X-linked adrenoleukodystrophy, pathophysiology, neurodegeneration, myelopathy, leukodystrophy, axons, glia, neuropathology, postmortem studies
MeSH terms
Adrenoleukodystrophy, Axons, Humans, Spinal Cord Diseases

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