Highlights
- •HDLS pathologically shows white matter degeneration and many axonal spheroids.
- •Axonal degeneration with spheroids is an early disease process in HDLS.
- •Axonal proteins and α-synuclein are involved in the spheroid formation.
Abstract
Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a neurodegenerative
disease clinically characterized by slowly progressive cognitive decline and motor
dysfunction. Neuropathology shows diffuse degeneration in the white matter, with prominent
presence of widespread axonal spheroids. To investigate the mechanism underlying HDLS
neurodegeneration, we characterized spheroids and examined their development in the
degenerated white matter. Analysis revealed that the spheroids are an early neuropathological
manifestation in the white matter degeneration and involve axonal component proteins
and α-synuclein. The development of spheroids facilitates in initiating neurodegeneration
in HDLS.
Keywords
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References
- Cytoskeleton.in: Molecular Biology of the Cell. 5th ed. Cytoskeleton. Garland Science, New York2008: 965-1052
- Hereditary diffuse leucoencephalopathy with spheroids.Acta Psychiatr Scand Suppl. 1984; 314: 1-65
- Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.Acta Neuropathol (Berl). 2006; 111: 300-311
- Degenerative diseases of the cerebral cortex and the white matter.in: Metabolic and degenerative diseases of the central nervous system: pathology, biochemistry, and genetics. Academic Press, San Diego1995: 497-519
- Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations.Brain Pathol. 2009; 19: 39-47
- Autosomal dominant leukodystrophy with axonal spheroids and pigmented glia: clinical and neuropathological characteristics.Acta Neuropathol (Berl). 2006; 111: 39-45
- Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature.Acta Neuropathol (Berl). 2004; 107: 481-488
- Clinical, pathological and neurochemical studies of a case of sudanophilic leukodystrophy.Psychiatr Neurol Jpn. 1971; 73 (906-7, in Japanese with English abstract): 840-853
- Microtubule depolymerization suppresses α-synuclein accumulation in a mouse model of multiple system atrophy.Am J Pathol. 2009; 174: 1471-1480
- Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.Nat Genet. 2011; 44: 200-205
- Neuropathological conditions related to neuroaxonal dystrophy.Acta Neuropathol (Berl). 1971; suppl V: 17-29
- Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): a misdiagnosed disease entity.J Neurol Sci. 2012; 314: 130-137
- β-III Tubulin fragments inhibit α-synuclein accumulation in models of multiple system atrophy.J Biol Chem. 2014; 289: 24374-24382
- Cystatin C triggers neuronal degeneration in a model of multiple system atrophy.Am J Pathol. 2014; 184: 790-799
- An autopsy case of hereditary diffuse leukoencephalopathy with spheroids, clinically suspected of Alzheimer's disease.Acta Neuropathol (Berl). 2004; 108: 538-545
- Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids.Neurology. 2000; 54: 463-468
- Cavitating “diffuse sclerosis”.J Neuropathol Exp Neurol. 1967; 26: 437-455
- Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): a single entity?.Neurology. 2009; 72: 1953-1959
- Long tract degeneration in familial sudanophilic leukodystrophy with prominent spheroids.J Neurol Sci. 1997; 147: 185-191
- Mouse model of multiple system atrophy: α-synuclein expression in oligodendrocytes causes glial and neuronal degeneration.Neuron. 2005; 45: 847-859
Article info
Publication history
Published online: March 27, 2015
Accepted:
March 18,
2015
Received in revised form:
February 16,
2015
Received:
December 8,
2014
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
