Phospholipids in X-linked adrenoleukodystrophy white matter: Fatty acid abnormalities before the onset of demyelination
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Changes in fatty acid composition of complex lipids were analyzed in postmortem white matter from a patient with late onset adrenoleukodystrophy (ALD). The specimen showed three regions with progressive myelin breakdown: morphologically normal white matter; areas with active demyelination and perivascular lymphocyte and macrophage infiltration; and areas with marked gliosis. In the morphologically intact region, cholesterol esters were similar in amount and fatty acid composition to those in control tissue, although marked changes were observed in the actively demyelinating area. Galactolipids in these areas were also similar to those in controls. In contrast, glycerophospholipids were increased in amount and in very long chain fatty acids (VLCFA), which are the hallmark of ALD, at the active edge of the demyelinative lesion and even in the apparently intact sample. Further fractionation of the glycerophospholipids by high performance liquid chromatography showed a significant (up to 39-fold) accumulation of hexacosanoic acid (C26:0) in phosphatidylcholine, but not in other phosphatidyl derivatives. The consistent increases in phosphatidylcholine VLCFA in all samples from the ALD brain, which are postulated to represent progressive stages in the development of the disorder, suggest that phosphatidylcholine may be involved in antigen formation and may underlie an immunological basis for the pathogenesis of ALD.
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White matter areas appearing histologically intact in cALD also show VLCFA accumulation in PC and more limited VLCFA increases in CEs.
“White matter areas appearing histologically intact also showed VLCFA accumulation in PC and more limited VLCFA increases in CEs.”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [163]
Abnormal VLCFA metabolism precedes demyelination in cALD.
“The authors concluded that abnormal VLCFA metabolism preceded demyelination [163,164] because CE-synthesis enzymes are ten times more active than CE-hydrolysis enzymes [165].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [163]
The white matter and myelin of actively demyelinating areas in cALD show major VLCFA accumulation in glycerolipids, notably phosphatidylcholine (PC) and cholesterol esters (CEs).
“The white matter and myelin of actively demyelinating areas showed major VLCFA accumulation in glycerolipids, notably phosphatidylcholine (PC) and cholesterol esters (CEs).”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [163]
Abnormal VLCFA (C > 22) accumulation was first documented in the brains of a young adult and five children with cALD.
“Abnormal VLCFA (C > 22) accumulation was first documented in the brains of a young adult and five children with cALD [163,164].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [163]
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Moser, H. W., Mahmood, A., & Raymond, G. V. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0421 · Cited by 663 · see citing works
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Moser, H. W., Mahmood, A., & Raymond, G. V. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0421 · Cited by 663 · see citing works
Self-citationX-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects
Kemp, S., Berger, J., & Aubourg, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.012 · Cited by 283 · see citing works
Pathophysiology of X-linked adrenoleukodystrophy
Berger, J., Forss-Petter, S., & Eichler, F. S. (2014) · Biochimie · doi:10.1016/j.biochi.2013.11.023 · Cited by 238 · see citing works
Peroxisomal Disorders: Genotype, Phenotype, Major Neuropathologic Lesions, and Pathogenesis
Powers, J. M., & Moser, H. W. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00139.x · Cited by 208 · see citing works
Self-citationHo, J. K., Moser, H., Kishimoto, Y., & Hamilton, J. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118182 · Cited by 199 · see citing works
Self-citationVery long chain fatty acids in higher animals: a review
Poulos, A. (1995) · Lipids · doi:10.1007/bf02537036 · Cited by 192 · see citing works
Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy?
Eichler, F. S., Ren, J., Cossoy, M., Rietsch, A. M., Nagpal, S., Moser, A. B., Frosch, M. P., & Ransohoff, R. M. (2008) · Annals of Neurology · doi:10.1002/ana.21391 · Cited by 178 · see citing works
Self-citationHein, S., Schonfeld, P., Kahlert, S., & Reiser, G. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn066 · Cited by 180 · see citing works
Ito, M., Blumberg, B. M., Mock, D. J., Goodman, A. D., Moser, A. B., Moser, H. W., Smith, K. D., & Powers, J. M. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.10.1004 · Cited by 125 · see citing works
Self-citationBiochemical aspects of X-linked adrenoleukodystrophy
Kemp, S., & Wanders, R. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00391.x · Cited by 116 · see citing works
Expression of the adrenoleukodystrophy protein in the human and mouse central nervous system
Fouquet, F., Zhou, J. M., Ralston, E., Murray, K., Troalen, F., Magal, E., Robain, O., Dubois-Dalcq, M., & Aubourg, P. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0127 · Cited by 115 · see citing works
Brain endothelial dysfunction in cerebral adrenoleukodystrophy
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 · doi:10.1093/brain/awv250 · Cited by 92 · see citing works
Self-citationMcGuinness, M. C., Powers, J. M., Bias, W. B., Schmeckpeper, B. J., Segal, A. H., Gowda, V. C., Wesselingh, S. L., Berger, J., Griffin, D. E., & Smith, K. D. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00020-9 · Cited by 89 · see citing works
Self-citationWeber, F. D., Wiesinger, C., Forss-Petter, S., Regelsberger, G., Einwich, A., Weber, W. H. A., Kohler, W., Stockinger, H., & Berger, J. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt645 · Cited by 63 · see citing works
Rattay, T. W., Rautenberg, M., Söhn, A. S., Hengel, H., Traschütz, A., Röben, B., Hayer, S. N., Schüle, R., Wiethoff, S., Zeltner, L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-71248-8 · Cited by 61 · see citing works
The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder
Hiebler, S., Masuda, T., Hacia, J. G., Moser, A. B., Faust, P. L., Liu, A., Chowdhury, N., Huang, N., Lauer, A., Bennett, J., et al. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.01.008 · Cited by 60 · see citing works
Self-citationPillai, B. K., Jasuja, R., Simard, J. R., & Hamilton, J. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.043737 · Cited by 27 · see citing works
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11 · see citing works
- Authors
- Theda, C., Moser, A. B., Powers, J. M., & Moser, H. W.
- Affiliations
- University of Maryland, Baltimore (US)
- Johns Hopkins University (US)
- Columbia University (US)
- Corresponding author
- Theda, Christiane
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 1992-07
- Volume
- 110
- Issue
- 1-2
- Pages
- 195-204
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W2021473352
- Cited by
- 99
- References
- 1
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the Neurological Sciences (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24061, P30HD024061)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- X-linked adrenoleukodystrophy, white matter demyelination, phospholipids, very long chain fatty acids, hexacosanoic acid, phosphatidylcholine, glycerophospholipids, cholesterol esters, galactolipids, gliosis, myelin breakdown, immunopathogenesis
- MeSH terms
- Adrenoleukodystrophy, Adult, Brain Chemistry, Cholesterol, Fatty Acids, Glycolipids, Humans, Lipids, Male, Myelin Sheath, Phospholipids, Reference Values, X Chromosome, Galactolipids
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