Alexander Disease

Tavasoli, Ali Reza; Armangué, Thaís; Ho, Cheng Ying; Whitehead, Matthew T.; Bornhorst, Miriam; Rhee, Jullie; Hwang, Eui-Hyoung; Wells, Elizabeth; Packer, Roger; Knaap, Marjo S. van der; Bugiani, Marianna; Vanderver, Adeline

doi:10.1177/0883073816673263

Cited by 14 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…AxD has presented in rare patients as a mass lesion, involving, for example, the brainstem or optic chiasm , suggesting the diagnosis of an astrocytoma. The Ki67 indices are low but raise above the lower levels present in the normal CNS.…”

Section: The Degree Of White Matter Pathology Varies and Predominatesmentioning

confidence: 99%

Alexander disease: an astrocytopathy that produces a leukodystrophy

2018

View full text Add to dashboard Cite

Alexander Disease (AxD) is a degenerative disorder caused by mutations in the GFAP gene, which encodes the major intermediate filament of astrocytes. As other cells in the CNS do not express GFAP, AxD is a primary astrocyte disease. Astrocytes acquire a large number of pathological features, including changes in morphology, the loss or diminution of a number of critical astrocyte functions and the activation of cell stress and inflammatory pathways. AxD is also characterized by white matter degeneration, a pathology that has led it to be included in the "leukodystrophies." Furthermore, variable degrees of neuronal loss take place. Thus, the astrocyte pathology triggers alterations in other cell types. Here, we will review the neuropathology of AxD and discuss how a disease of astrocytes can lead to severe pathologies in non-astrocytic cells. Our knowledge of the pathophysiology of AxD will also lead to a better understanding of how astrocytes interact with other CNS cells and how astrocytes in the gliosis that accompanies many neurological disorders can damage the function and survival of other cells.

show abstract

Section: The Degree Of White Matter Pathology Varies and Predominatesmentioning

confidence: 99%

Alexander disease: an astrocytopathy that produces a leukodystrophy

2018

View full text Add to dashboard Cite

show abstract

“…При юношеской форме демиелинизация по данным МРТ выявляется преимущественно в лобных областях, при взрослых формах -в области мозжечка и ствола головного мозга [7].…”

Section: к л и н и ч е с к и е н а б л ю д е н и яunclassified

Juvenile form of alexander disease caused by a previously undescribed mutation in the GFAP gene. a case report

Павлючкова

Котов

2021

Rus. ž. det. nevrol.

View full text Add to dashboard Cite

Alexander disease is a form of leukoencephalopathy caused by mutations in the GFAP gene. There are three forms of the disease: infant, juvenile and adult. We present the clinical case of a patient born in 2004 (16 years old) with a debut of the disease at the age of 4 years with complex ticks. further neurological symptoms progressed and appeared atactic gait, intention tremor by performing coordination tests, muscle hypotension, decreased tendon reflexes, nasal voices, and behavior changes.Magnetic resonance imaging revealed changes in the white matter of both frontal lobes. An analysis was made of 59 genes of the panel “Leukodystrophy/leukoencephalopathy” by the method of mass parallel sequencing on the Ion S5. A mutation of the GFAP gene (Nm_002055), 4 exon c.758C>A, p.ALA253Asp in a heterozygous state, not described in Human Gene mutation Database, was detected. The patient was confirmed to have a diagnosis of Alexander disease. According to tractography, a decrease in the number of fibers in the frontal lobes was found.The patient is currently receiving symptomatic treatment.

show abstract

“…Alexander disease (AxD) is a rare but devastating disease that affects neural development and causes ataxia, seizures, intellectual dysfunction, and many other disabilities 1,2 . It is caused by heterozygous pathogenic variants of the Glial Fibrillary Acidic Protein (GFAP), 3–5 which codes for a major intermediate filament protein expressed exclusively in astrocytes within the brain.…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, ex vivo diffusion magnetic resonance imaging (MRI) has advantages over in vivo diffusion MRI in terms of a high signal‐to‐noise ratio and spatial resolution 34 . Although some neuroimaging studies have reported MRI features, particularly leukodystrophic features, of AxD, 2 to the best of our knowledge, no study has assessed brain pathways in AxD. Therefore, little is known about brain connectivity in AxD.…”

Section: Introductionmentioning

confidence: 99%

Identification of association fibers using ex vivo diffusion tractography in Alexander disease brains

Shiohama

Stewart

Nangaku

et al. 2022

Journal of Neuroimaging

View full text Add to dashboard Cite

Background and Purpose: Alexander disease (AxD) is a neurodegenerative disorder caused by heterozygous Glial Fibrillary Acidic Protein mutation. The characteristic structural findings of AxD, such as leukodystrophic features, are well known, while association fibers of AxD remain uninvestigated. The aim of this study was to explore global and subcortical fibers in four brains with AxD using ex vivo diffusion tractography Methods: High-angular-resolution diffusion magnetic resonance imaging (HARDI) tractography and diffusion-tensor imaging (DTI) tractography were used to evaluate long and short association fibers and compared to histological findings in brain specimens obtained from four donors with AxD and two donors without neurological disorders Results: AxD brains showed impairment of long association fibers, except for the arcuate fasciculus and cingulum bundle, and abnormal trajectories of the inferior longitudinal and fronto-occipital fasciculi on HARDI tractography and loss of multidirectionality in subcortical fibers on DTI tractography. In histological studies, AxD brains showed diffuse low density on Klüver-Barrera and neurofilament staining and sporadic Rosenthal fibers on hematoxylin and eosin staining Conclusions: This study describes the spatial distribution of degenerations of short and long association fibers in AxD brains using combined tractography and pathological findings.

show abstract

Alexander Disease

Cited by 14 publications

References 16 publications

Alexander disease: an astrocytopathy that produces a leukodystrophy

Alexander disease: an astrocytopathy that produces a leukodystrophy

Juvenile form of alexander disease caused by a previously undescribed mutation in the GFAP gene. a case report

Identification of association fibers using ex vivo diffusion tractography in Alexander disease brains

Contact Info

Product

Resources

About