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M Tabaton

Publications and source records attributed to M Tabaton.

At least 55 records · Page 3Linked to original sources
PubMed1994

Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy).

We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.

Brain↗
PubMed1994

Research advances in the biology of Alzheimer's disease.

Research on AD has shed light on the biochemical composition and mechanisms of the formation of amyloid deposits and PHFs, the structural hallmarks of the disease. Amyloid is composed of a 4-kd peptide, beta P, that originates in the metabolism of a 130-kd transmembrane precursor protein. Soluble beta P accumulates in the AD brain until it polymerizes in amyloid fibers. Paired helical filaments are composed of hyperphosphorylated tau, a microtubule-associated protein that normally acts as a tubulin assembly factor. Future research must clarify why beta P accumulates in extracellular spaces of AD tissue and focus on the relation between amyloid deposition and neuronal degeneration.

Alzheimer Disease↗
PubMed1993

Ubiquitin-reactive neurites in cerebral cortex of subjects with Huntington's chorea: a pathological correlate of dementia?

We studied the prevalence of ubiquitin-reactive dystrophic neurites in neocortex of cases with Huntington's disease (HD), with a history of dementia lasting from 5 to 8 years before death, and in four age-matched controls. The ubiquitin-reactive neurites, identified as round structures localized outside neuronal and glial cells, were quantified in six microscopic fields of cingulate, 2nd temporal and 2nd parietal cortical gyri. The number of ubiquitin-reactive neurites in HD was 12 to 16 times that of controls in the three cortical areas examined. The finding indicates that in HD neocortex there is a severe degeneration of neuronal processes and suggests that it may represent a pathological correlate of dementia.

Aged↗
PubMed1992

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism.

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism.

Adult↗
PubMed1992

Senile plaques in cerebral amyloid angiopathy show accumulation of amyloid precursor protein without cytoskeletal abnormalities.

The abnormal neurites that surround beta-amyloid in senile plaques (SP) in Alzheimer disease contain beta-amyloid precursor protein (beta APP) or abnormal filaments which react with antibodies to tau. Occasionally, beta APP and abnormal filaments are present in the same neurite. Whether both types of abnormal neurites are reactive to the presence of beta-amyloid or they are instead independent from each other is unknown. To begin to clarify this issue, we comparatively studied beta APP and tau-epitopes in SP from cases of classical Alzheimer disease and cases of cerebral amyloid angiopathy, with SP but without neurofibrillary pathology. In subjects with cerebral amyloid angiopathy, about one-third of SP, the same percentage as in Alzheimer disease, were beta APP reactive in the absence of tau-reactivity. beta APP epitopes were ultrastructurally localized in dense bodies of probable lysosomal origin, adjacent to the core of SP. These results demonstrate that beta APP and tau-reactive cytoskeletal alterations occur independently in the neurites of SP. The presence of beta APP in dystrophic neurites of SP and the localization of beta APP in lysosomes suggest that beta APP containing dystrophic neurites may play a role in the extracellular deposition of amyloid.

Alzheimer Disease↗
PubMed1992

GFAP expression of human Schwann cells in tissue culture.

We have studied the expression of the intermediate filament (IF) proteins, vimentin and glial fibrillary acidic protein (GFAP), in cultured human Schwann cells (SC) from patients with different neuropathies and normal control cases. SC cultures from sural nerve biopsies of 8 subjects with axonal neuropathies, 8 with demyelinating neuropathies and 3 normal controls were included in this study and processed with double immunofluorescence technique, using anti-vimentin and anti-GFAP antibodies, during the 2nd, 4th and 6th week of culture. Five cultures incubated with anti-GFAP antibodies were also processed for immunoelectron microscopy. Specificity tests of the used antibodies were performed. We have found that: (1) cultured human SC constantly express vimentin; (2) SC from normal controls are GFAP-negative in the first period of culture; (3) SC from pathologic nerves can contain GFAP-immunoreactive IF and the percentage of GFAP-positive SC is higher in axonal than in demyelinating neuropathies; (4) during the permanence in culture human SC from both normal and pathologic cases acquire the ability to synthesize GFAP. The obtained data suggest that the removal from axonal contact and the resulting loss of myelinating function induce a cytoskeletal cellular response in human SC characterized by the cytoplasmic accumulation of GFAP-immunoreactive IF.

Antibody Specificity↗
PubMed1992

Ubiquitin-reactive axons have a widespread distribution and are unrelated to prion protein plaques in Creutzfeldt-Jakob disease.

The amyloid plaques of Alzheimer disease (AD) are surrounded by dystrophic axons that contain ubiquitinated dense bodies. To investigate whether deposits of other types of amyloid cause axonal degeneration we studied 5 cases of Creutzfeldt-Jakob disease (CJD) with immunocytochemical methods using ubiquitin and prion protein (PrP) antisera. One of these cases contained PrP plaques in the cerebellum. In all cases dystrophic axons, which contain ubiquitinated dense bodies, were observed in neocortical and cerebellar grey matter, in absence of PrP-reactive amyloid deposits. Only a minority of PrP plaques present in the cerebellum was associated with ubiquitin positive neurites. The results indicate that, unlike in AD, the occurrence of ubiquitinated dystrophic axons is independent from amyloid deposition in CJD and is likely to be a primary phenomenon.

Aged↗
PubMed1992

Hereditary motor and sensory neuropathy with deafness, mental retardation and absence of large myelinated fibers.

Two brothers with a presumably hereditary motor and sensory polyneuropathy (HMSN), sensory-neural hearing loss and mental retardation had clinical features and neuropathological changes in the sural nerve which may set the disorder apart from previously described types of HMSN. Consecutive sural nerve biopsies from one case showed absence of large myelinated fibers and a normal complement of small fibers. We infer from our findings that a developmental abnormality with faulty growth and subsequent axonal atrophy may be responsible.

Adolescent↗
PubMed1992

Analysis of the prion protein gene in thalamic dementia.

Thalamic degenerations or dementias are poorly understood conditions. The familial forms are (1) selective thalamic degenerations and (2) thalamic degenerations associated with multiple system atrophy. Selective thalamic degenerations share clinical and pathologic features with fatal familial insomnia, an autosomal dominant disease linked to a mutation at codon 178 of the prion protein (PrP) gene that causes the substitution of asparagine for aspartic acid (178Asn mutation). We amplified the carboxyl terminal coding region of the PrP gene from subjects with selective thalamic dementia or thalamic dementia associated with multiple system atrophy. Three of the four kindreds with selective thalamic dementia and none of the three kindreds with thalamic dementia associated with multiple system atrophy had the PrP 178Asn mutation. Thus, analysis of the PrP gene may be useful in diagnosing the subtypes of thalamic dementia. Moreover, since selective thalamic dementia with the PrP 178Asn mutation and fatal familial insomnia share clinical and histopathologic features, we propose that they are the same disease.

Base Sequence↗
PubMed1992

Subcellular localization of amyloid precursor protein in senile plaques of Alzheimer's disease.

The authors have previously shown that amyloid precursor protein (APP) accumulates in neurites present in senile plaques of Alzheimer's disease (AD). In this ultrastructural immunocytochemical study, we describe the subcellular site of APP accumulation. Vibratome sections of glutaraldehyde-paraformaldehyde fixed hippocampi from five cases of AD were pretreated with methanol and immunostained with an antibody raised against recombinant APP 770 by using either indirect immunogold or peroxidase methods. Immunolabeling was localized in cell processes filled with amorphous, irregular-shaped materials, which were identified as dense bodies deformed by postmortem autolysis and methanol treatment, as well as multilamellar membranous bodies. Identification of these bodies was obtained with comparative ultrastructural examination of biopsy and autopsy tissue fixed with and without methanol treatment. These electron-dense organellae were positive for the lysosomal marker, acid phosphatase. At light microscopy, acid phosphatase and APP colocalized to the same cell processes in senile plaques. Many of those cell processes contained abnormal straight or paired helical filaments supporting their neuritic nature. These results suggest that APP accumulates in the lysosomal system of the dystrophic neurites present in senile plaques and are consistent with a neuronal origin of the APP forming the amyloid in senile plaques.

Acid Phosphatase↗
PubMed1992

Beta protein immunoreactivity is found in the majority of neurofibrillary tangles of Alzheimer's disease.

The presence of dystrophic neurites in most extracellular neurofibrillary tangles (E-NFT) suggests a factor promoting neurite growth in E-NFT. Although the beta-protein detected in E-NFT may fill that role, reports that only 2-10% of E-NFT contain beta-protein whereas 80-100% contain dystrophic neurites suggested that beta-protein does not play an important role. In this study, the authors used two antisera and one monoclonal antibody to beta-protein to establish the effects of tissue preparation and formic acid enhancement on the detection of beta-protein in E-NFT. We found that beta-protein epitopes in E-NFT are sensitive to formaldehyde fixation and are best enhanced by 50% formic acid, whereas beta-protein in senile plaques is best enhanced at higher formic acid concentrations. After treatment with 50% formic acid, beta-protein was found in all E-NFT. Interestingly, after treatment with 10% formic acid, half of intraneuronal-NFT (I-NFT) also contained beta-protein immunoreactivity. The finding that beta-protein immunoreactivity in senile plaques, E-NFT and I-NFT is increased at different formic acid concentrations suggests that beta-protein in each location is in a different conformation. In contrast, no beta-protein immunoreactivity could be found in E-NFT of the brain stem, an area in which dystrophic neurites do not infiltrate E-NFT. These findings indicate a correlation between neuritic infiltration and presence of beta-protein in E-NFT and suggests the two are linked in Alzheimer's disease for E-NFT as well as senile plaques.

Aged↗
PubMed1991

Dystrophic neurites infiltrate extracellular neurofibrillary tangles in Alzheimer disease.

The neurotrophic activity of beta-amyloid protein (beta-AP) has been suggested to be responsible for the dystrophic neurites that surround beta-AP deposits in senile plaques of Alzheimer disease. The recent finding that neurofibrillary tangles (NFT) that remain as remnants in the extracellular space (E-NFT) after the death of the neuron contain beta-AP, suggested that dystrophic neurites might also be associated with E-NFT. In this study, we use a probe for E-NFT, basic fibroblast growth factor (bFGF)-binding to show that E-NFT do contain dystrophic neurites. Since these neurites contain the amyloid precursor protein whose cleavage can lead to beta-AP, they may also play a role in further beta-AP deposition in the E-NFT.

Aged↗
PubMed1991

Demonstration of a novel neurofilament associated antigen with the neurofibrillary pathology of Alzheimer and related diseases.

A monoclonal antibody, termed NFT200, was raised after in vitro immunization with sonicated neurofibrillary tangle (NFT)-enriched fractions prepared from Alzheimer brain. The antigen to which NFT200 is directed was expressed in the paired helical filaments of NFT in sporadic and familial Alzheimer disease (AD), in the straight filaments of NFT in AD, progressive supranuclear palsy and of Pick bodies, and the NFT in several other conditions such as Parkinson-dementia complex of Guam and subacute sclerosing panencephalitis. Granulovacuolar degeneration of AD was also labeled with NFT200. Hirano bodies and amyloid deposits in AD, as well as Lewy bodies of idiopathic Parkinson disease lacked in the antigen. The NFT200-antigen was also expressed as a phosphatase-insensitive antigen in normal neurofilaments found in spinal cord and peripheral nerve axons but was absent from the perikaryal accumulation of neurofilaments induced by aluminum intoxication. Nevertheless, immunoblot studies failed to detect the NFT200 in isolated preparations of the neurofilament proteins, MAP-2, tau, ubiquitin or A4-amyloid peptide. The results indicate that the NFT200 monoclonal antibody is directed against a phosphatase-insensitive epitope of an axonal protein associated with neurofilaments but is labile to isolation and expressed as a stable epitope of a 200 kDa component of NFT.

Alzheimer Disease↗
PubMed1991

Ultrastructural localization of beta-amyloid, tau, and ubiquitin epitopes in extracellular neurofibrillary tangles.

Neurofibrillary tangles (NFTs), a hallmark of Alzheimer disease, are commonly located in perikarya of neurons. In advanced cases of Alzheimer disease, however, NFTs are observed also in the extracellular space. As extracellular NFTs (E-NFTs), and occasionally intracellular NFTs (I-NFTs), are recognized by antibodies to beta-amyloid protein (beta AP), beta AP may be present not only in amyloid deposits but also in paired helical filaments (PHFs), the primary components of NFTs. We compared the antigenic characteristics of I-NFTs and E-NFTs with light- and electron-microscopic immunocytochemistry by using several antibodies to noncontiguous epitopes of the microtubule-associated protein tau and of ubiquitin (Ub) as well as an antiserum to beta AP. At variance with I-NFTs, E-NFTs were made predominantly of straight filaments (SFs), rather than PHFs, that were often separated by astroglial processes and in close association with small beta AP deposits. Occasionally, E-NFTs were made of bundles of amorphous material, which showed no resemblance to SFs, PHFs, or amyloid fibrils. The antigenic changes in E-NFTs suggest that when NFTs become extracellular they lose the N and, possibly, the C termini of tau while maintaining the intermediate region of the molecule; they also lose the N-terminal two-thirds of Ub while the C-terminal conjugation site of Ub is preserved. A small subset of E-NFTs reacted with antibodies to both beta AP and tau. Although in most E-NFTs, the epitopes recognized by tau and Ub antibodies were located in typical PHFs and SFs, the epitopes recognized in this subset of anti-beta AP and anti-tau-positive E-NFTs were located exclusively in the bundles of amorphous material. It is suggested that either beta AP epitopes are present but inaccessible in PHFs and SFs and become exposed after conformational changes occurring in the extracellular space or PHFs and SFs become closely associated with beta AP in the extracellular space.

Alzheimer Disease↗
PubMed1991

Motor and sensory evoked potentials in progressive supranuclear palsy.

Motor potentials evoked in the biceps, thenar, and tibialis anterior muscles by electrical stimulation of the scalp and of the spinal regions were recorded in 12 patients with progressive supranuclear palsy (PSP) and in a control group. Abnormalities of central motor conduction for at least one muscle were present in five patients (41.7%), characterized by a long illness duration. The central sensory conduction time of the median nerve was normal, but five patients showed a depressed frontal N30 wave. These findings support the possible occurrence of functional damage to the corticospinal tracts and to the supplementary motor area in PSP.

Aged↗
PubMed1991

Schwann cell GFAP expression increases in axonal neuropathies.

We studied the Schwann cell (SC) GFAP immunoreactivity in normal human peripheral nerves and in neuropathies of different origin. Immunofluorescence and immunocytochemistry were carried out on serial frozen sections of 58 peripheral nerve biopsies using monoclonal antibodies (mabs) antivimentin and anti GFAP, and antiserum anti S-100 and anti GFAP. To test the specificity of the mabs and antiserum used, proper competition controls on tissue sections of 2 selected cases, tissue cultures studies of human fibroblasts and immunoblotting of homogenates of human fibroblasts, 3 normal and 5 pathologic nerves were carried out. In order to evaluate a possible correlation between SC GFAP positivity and neuropathologic findings a quantitative study was performed, evaluating the SC GFAP reactivity in all the 58 cases, and relating the SC GFAP positivity to the index of nerve pathology (IP) in 9 selected cases, and to the percentage of teased fibers showing axonal degeneration or demyelination and remyelination in 25 representative cases. We demonstrate that in normal human sural nerves and in demyelinating neuropathies only a few scattered SC are recognized by the mabs or antiserum anti GFAP. On the contrary in axonal neuropathies the majority of SC gain the property to express intermediate filaments which show common antigenic properties with GFAP.

Antibodies, Monoclonal↗
PubMed1991

Amyloid beta protein deposition in brains from elderly subjects with leukoaraiosis.

We studied immunocytochemically with 2 amyloid beta protein (ABP) antisera brains from 5 non-demented elderly subjects with evidence of diffuse periventricular white matter hypodensity on computed tomography. In periventricular white matter of all brains we found ABP reactive deposits arranged around small vessels walls. Furthermore ABP reactive deposits, identical to those currently called diffuse plaques, were detected in neocortex in amount proportional to that of white matter deposits. We suggest that ABP microangiopathy and parenchymal deposition is responsible of white matter rarefaction in a subset of cases with a diffuse hypodensity on CT scan which has been called leukoaraiosis.

Aged↗