Multimodal quantitative MRI finds early brain changes in asymptomatic X-linked adrenoleukodystrophy
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ID: 327308
2026
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Abstract
Abstract Adrenoleukodystrophy (ALD) is an X-linked recessive disease caused by defects in the ABCD1 gene, leading to the accumulation of very long chain fatty acids in the nervous system, adrenal glands, blood, and other tissues. Male ALD patients may present with either the severe neurological phenotype of cerebral ALD, characterized by inflammatory demyelination in the white matter and rapid neurological deterioration, or milder forms such as adrenomyeloneuropathy. We aimed to identify early brain changes in asymptomatic ALD patients prior to the clinical onset of cerebral ALD or adrenomyeloneuropathy by exploratory analysis of multimodal MRI data. Multimodal MRI data - including structural images, diffusion tensor imaging, magnetization transfer imaging, and MR spectroscopy – were obtained from asymptomatic ALD patients during regular follow-up MRIs. Longitudinal MRI data were analyzed from 12 asymptomatic ALD patients aged 10 to 18 years who did not develop a cerebral ALD phenotype during our surveillance and from 12 healthy age-matched male controls. Volumetric analyses of brain structures were performed using structural MRI data, as well as region-of-interest measurements on diffusion tensor imaging, magnetization transfer imaging, and MR spectroscopy data. Statistical analysis was performed using linear mixed effects models. Volumetry indicated increased white matter volume in asymptomatic ALD patients. Diffusion tensor imaging analysis revealed increased values of radial and mean diffusivity in the supratentorial white matter. Magnetization transfer saturation values derived from magnetization transfer imaging metrics were increased in the cortical and subcortical gray matter, but not in the white matter. MR spectroscopy showed increased inositol levels in the frontal white matter. Our diffusion tensor imaging and MR spectroscopy data indicate early white matter pathology in adolescent asymptomatic ALD patients. Among these findings, increased white matter volume and, in addition, elevated magnetization transfer saturation values in the gray matter are novel MRI phenotypes associated with asymptomatic ALD. These results suggest that not only white matter but also gray matter can be pathologically altered even before the onset of neurological phenotypes. Multimodal MRI parameters therefore constitute promising biomarkers for the assessment of pre-symptomatic brain tissue alterations in ALD and may be useful in future clinical studies targeting early therapeutic intervention.
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| Authors | Kolja Meier, Prativa Sahoo, Lara M. Marten, Irini Gkalimani, Gunther Helms, Peter Dechent, Hendrik Rosewich, Steffi Dreha-Kulaczewski, Jutta Gärtner |
| Journal | Brain communications |
| Year | 2026 |
| DOI |
10.1093/braincomms/fcag311
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| URL | |
| Keywords | Keywords not found |
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