FUS pathology in basophilic inclusion body disease

  title={FUS pathology in basophilic inclusion body disease},
  author={David G Munoz and Manuela Neumann and Hirofumi Kusaka and Osamu Yokota and Kenji Ishihara and Seishi Terada and Shigetoshi Kuroda and Ian R A Mackenzie},
  journal={Acta Neuropathologica},
Basophilic Inclusion Body Disease (BIBD) is a tau-negative form of frontotemporal lobar degeneration (FTLD), characterized by neuronal cytoplasmic inclusions (NCI) that are visible on hematoxylin and eosin stain (HE), contain RNA, and are inconsistently ubiquitin-immunoreactive (ir). The normal nuclear expression of TDP-43 is not altered. Here we investigate whether the distribution of the structurally and functionally related protein fused in sarcoma (FUS) is altered in BIBD. Mutations in the… 

Neuronal intermediate filament inclusion disease may be incorrectly classified as a subtype of FTLD-FUS.

While FUS pathology remains a prominent feature of aFTLD-U, there is pathologic heterogeneity, including rare cases of NIFID with TDP-43- rather than FUS-positive inclusions.

Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations

Juvenile ALS with basophilic inclusions is a FUS proteinopathy and should be classified as ALS-FUS, and a novel deletion mutation and two mutations associated with this distinct phenotype are identified.

An autopsied case of sporadic adult‐onset amyotrophic lateral sclerosis with FUS‐positive basophilic inclusions

Immunohistochemically and ultrastructurally studied an autopsy case of sporadic adult‐onset ALS with numerous BIs and found that both Betz cells in the motor cortex and motor neurons in the spinal cord were affected.

Distinct pathological subtypes of FTLD-FUS

Findings support aFTLD-U, NIFID and BIBD as representing closely related, but distinct entities that share a common molecular pathogenesis.

Pathological features of FTLD-FUS in a Japanese population: Analyses of nine cases

FUS/TLS-Immunoreactive Neuronal and Glial Cell Inclusions Increase With Disease Duration in Familial Amyotrophic Lateral Sclerosis With an R521C FUS/TLS Mutation

The distribution of FUS/TLS-immunoreactive inclusions in FUS-mutated FALS with BIs was broader than that of BIs alone, suggesting that the pathogenetic mechanism may have originated from the FUS /TLS proteinopathy.

Chorea as a clinical feature of the basophilic inclusion body disease subtype of fused-in-sarcoma-associated frontotemporal lobar degeneration

Three cases of the behavioral variant of frontotemporal dementia (bvFTD) that display chorea with fused in sarcoma (FUS)-positive inclusions (FTLD-FUS) and the basophilic inclusion body disease (BIBD) subtype are identified.

The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease

A quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG, and significantly more NCI revealed by FUS than α-internexin IHC.

Novel Types of Frontotemporal Lobar Degeneration: Beyond Tau and TDP-43

The discovery that the pathological changes in atypical FTLD with ubiquitinated inclusions, neuronal intermediate filament inclusion disease, and basophilic inclusion body disease are immunoreactive for the fused in sarcoma (FUS), resulting in the creation of a new molecular subgroup (FTLD-FUS).

Optineurin is co-localized with FUS in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease

The fact that both FUS and OPTN cause ALS when mutated prompted us to investigate the correlation between these proteins, and postmortem material from three patients with sporadic BIBD and three with FALS with FUS mutation was analyzed.



Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease

Findings suggest that FUS may play an important role in the pathogenesis of NIFID, and double-label immunofluorescence confirmed that many cells had only FUS- positive inclusions and that all cells with IF-positive inclusions also contained pathological FUS.

A new subtype of frontotemporal lobar degeneration with FUS pathology.

Findings suggest that FUS is the pathological protein in a significant subgroup of sporadic FTD and reinforce the concept that FTd and amyotrophic lateral sclerosis are closely related conditions.

Basophilic inclusion body disease and neuronal intermediate filament inclusion disease: a comparative clinicopathological study

The clinical features and distribution of neuronal loss are similar in BIBD and NIFIDs, and an unknown protein besides α-internexin and neurofilament may play a pivotal pathogenetic role in at least some NIFID cases.

Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions.

Six cases of early onset FTD with FTLD-U pathology that was negative for TDP-43 are described, believing that these cases represent a new entity that is clinically and pathologically distinct from all currently recognized subtypes of FTLD.

Neuropathologic Features of Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions Visualized With Ubiquitin-Binding Protein p62 Immunohistochemistry

Genetic, clinical, and neuropathologic heterogeneity have been observed in frontotemporal lobar degeneration with ubiquitin (Ubq)-positive inclusions (FTLD-U) and FTLD-U with motor neuron disease.

TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Frontotemporal lobar degeneration with ubiquitin-positive, but TDP-43-negative inclusions

Three cases of FTLD with ubiquitin- and p62-positive neuronal cytoplasmic inclusions confirmed the existence of TDP-43-negative FTLD-U and extend the clinical and pathological spectrum of this disorder.

Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity.

It is concluded that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms.

TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions.

The studies confirm that the spectrum of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FTD with charged multivesicular body protein 2B mutations.

Basophilic cytoplasmic inclusions in a case of sporadic juvenile amyotrophic lateral sclerosis