Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease

  title={Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease},
  author={Manuela Neumann and Sigrun Roeber and Hans A. Kretzschmar and Rosa Rademakers and Matt C. Baker and Ian R A Mackenzie},
  journal={Acta Neuropathologica},
Neuronal intermediate filament inclusion disease (NIFID) is an uncommon neurodegenerative condition that typically presents as early-onset, sporadic frontotemporal dementia (FTD), associated with a pyramidal and/or extrapyramidal movement disorder. The neuropathology is characterized by frontotemporal lobar degeneration with neuronal inclusions that are immunoreactive for all class IV intermediate filaments (IF), light, medium and heavy neurofilament subunits and α-internexin. However, not all… 

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.

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.

Spatial patterns of FUS-immunoreactive neuronal cytoplasmic inclusions (NCI) in neuronal intermediate filament inclusion disease (NIFID)

The spatial patterns of the FUS-immunoreactive NCI suggest the degeneration of the cortico-cortical projections in NIFID, which is similar spatial patterns to analogous inclusions in the tauopathies and synucleinopathies.

An autopsy case of neuronal intermediate filament inclusion disease with regard to immunophenotypic and topographical analysis of the neuronal inclusions

The above findings suggest that cytoplasmic mislocalization and aggregation of FUS appear at the early stage of the disease, and the FUS aggregate process may not be a direct precedent structure of HC.

FUS pathology in basophilic inclusion body disease

The consistent involvement of motorneurons in BIBD indicates that the association of FTLD and MND/ALS can occur on a FUS or TDP-43 pathological substrate, and together comprise a new biochemical category of neurodegenerative disease (FUS proteinopathies).

FUS‐Immunoreactive Intranuclear Inclusions in Neurodegenerative Disease

In a cell culture model of Huntington's disease, NIIs were intensely FUS‐positive and NII‐bearing cells displayed loss of the normal diffuse nuclear pattern of FUS staining, suggesting that sequestration of nuclear FUS by NIIs may interfere with its normal nuclear localization.

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.

FUS Immunogold Labeling TEM Analysis of the Neuronal Cytoplasmic Inclusions of Neuronal Intermediate Filament Inclusion Disease: A Frontotemporal Lobar Degeneration with FUS Proteinopathy

It is shown that FUS becomes relatively insoluble in NIFID and there is no apparent posttranslational modifications, there are no pathogenic abnormalities in the FUS gene in NifID, and immunoelectron microscopy demonstrates the fine structural localization of FUS in N IFID which has not previously been described.

Characteristic Features of FUS Inclusions in Spinal Motor Neurons of Sporadic Amyotrophic Lateral Sclerosis.

A novel detection method using a conventional antigen retrieval technique with Sudan Black B treatment to identify FUS-positive inclusions in sALS patients and classified pathological motor neurons into 5 different categories according to the different aggregation characteristics of FUS and TDP-43.

Neuronal intermediate filament inclusion disease.

  • N. Cairns
  • Medicine, Biology
    Handbook of clinical neurology
  • 2008



alpha-internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease.

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.

α-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases

The results indicate that class IV IF proteins are present within the pleomorphic inclusions of all cases of NIFID and small subsets of abnormal neuronal inclusions in Alzheimer’s disease, Lewy body diseases, and motor neuron disease also contain epitopes of α-internexin.

Screening for neurofilament inclusion disease using α-internexin immunohistochemistry

The frequency of NFID is investigated using α-internexin immunohistochemistry in 92 cases that had been diagnosed neuropathologically as FTLD, ALS, PLS, or MSA but in which routine screening with immunohISTochemistry for NF had not been previously done.

Neurofilament inclusion body disease with early onset frontotemporal dementia and primary lateral sclerosis.

This case confirms that NIBD should be considered in the differential diagnosis of FTD, particularly in young patients, and extends the clinical phenotype of NIBd to include PLS and better defines the anatomical distribution and morphology of the pathological lesions.

Clinical and pathological heterogeneity of neuronal intermediate filament inclusion disease.

These 2 cases confirm the clinical and pathological heterogeneity of NIFID and suggest its inclusion in the differential diagnosis of several neurodegenerative disorders, including frontotemporal dementia and atypical parkinsonism.

Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease

NIIs of NIFID contain filaments morphologically and immunologically distinct from those of NCIs, and both types of inclusion lack expanded polyglutamine tracts of the triplet-repeat expansion diseases.

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.

Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID)

Patients with a novel neurofilamentopathy: dementia with neurofilament inclusions