Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy

Paul J. Orchard, Todd W. Markowski, Lee Ann Higgins, Gerald Raymond, David R. Nascene, Weston P. Miller, Elizabeth I. Pierpont, Troy C. Lund

Research output: Contribution to journalArticle

Abstract

Cerebral adrenoleukodystrophy (cALD) is an inflammatory neurodegenerative disease associated with mutation of the ABCD1 gene. Proteomic analysis of cerebral spinal fluid (CSF) from young males with active cALD revealed markers of inflammation including APOE4. APOE4 genotype has been associated with an inferior prognosis following acute and chronic neurologic injury. We assessed APOE4 inheritance among 83 consecutive young males with cALD prior to hematopoietic cell transplant and its association with markers of cerebral disease. The allele frequency of APOE4 was not significantly different from that of the general population at 17%. Young males with cALD that were APOE4 carriers had similar CSF protein and chitotriosidase activity to that of non-carriers. In contrast, APOE4 carriers had an increased burden of cerebral disease involvement as determined by MRI severity score (10.5 vs 7.0 points, p = 0.01), higher gadolinium intensity score (2.0 vs 1.3 points, p = 0.007), inferior neurologic function (neurologic function score 2.4 vs 1.0, p = 0.001), and elevated CSF MMP2 levels compared to that of non-carriers (13168 vs 9472 pg/mL, p = 0.01). These are the first data showing that APOE4 is associated with increased severity of cerebral disease in cALD and suggest it may be a modifier of disease.

Original languageEnglish (US)
Article number7858
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Adrenoleukodystrophy
Biomarkers
Nervous System
Nervous System Trauma
Gadolinium
Gene Frequency
Neurodegenerative Diseases
Proteomics
Genotype
Inflammation
Transplants
Mutation
Population
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Orchard, P. J., Markowski, T. W., Higgins, L. A., Raymond, G., Nascene, D. R., Miller, W. P., ... Lund, T. C. (2019). Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy. Scientific reports, 9(1), [7858]. https://doi.org/10.1038/s41598-019-44140-3
Orchard, Paul J. ; Markowski, Todd W. ; Higgins, Lee Ann ; Raymond, Gerald ; Nascene, David R. ; Miller, Weston P. ; Pierpont, Elizabeth I. ; Lund, Troy C. / Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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abstract = "Cerebral adrenoleukodystrophy (cALD) is an inflammatory neurodegenerative disease associated with mutation of the ABCD1 gene. Proteomic analysis of cerebral spinal fluid (CSF) from young males with active cALD revealed markers of inflammation including APOE4. APOE4 genotype has been associated with an inferior prognosis following acute and chronic neurologic injury. We assessed APOE4 inheritance among 83 consecutive young males with cALD prior to hematopoietic cell transplant and its association with markers of cerebral disease. The allele frequency of APOE4 was not significantly different from that of the general population at 17{\%}. Young males with cALD that were APOE4 carriers had similar CSF protein and chitotriosidase activity to that of non-carriers. In contrast, APOE4 carriers had an increased burden of cerebral disease involvement as determined by MRI severity score (10.5 vs 7.0 points, p = 0.01), higher gadolinium intensity score (2.0 vs 1.3 points, p = 0.007), inferior neurologic function (neurologic function score 2.4 vs 1.0, p = 0.001), and elevated CSF MMP2 levels compared to that of non-carriers (13168 vs 9472 pg/mL, p = 0.01). These are the first data showing that APOE4 is associated with increased severity of cerebral disease in cALD and suggest it may be a modifier of disease.",
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Orchard, PJ, Markowski, TW, Higgins, LA, Raymond, G, Nascene, DR, Miller, WP, Pierpont, EI & Lund, TC 2019, 'Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy', Scientific reports, vol. 9, no. 1, 7858. https://doi.org/10.1038/s41598-019-44140-3

Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy. / Orchard, Paul J.; Markowski, Todd W.; Higgins, Lee Ann; Raymond, Gerald; Nascene, David R.; Miller, Weston P.; Pierpont, Elizabeth I.; Lund, Troy C.

In: Scientific reports, Vol. 9, No. 1, 7858, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Orchard, Paul J.

AU - Markowski, Todd W.

AU - Higgins, Lee Ann

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AU - Miller, Weston P.

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