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P Cras

Publications and source records attributed to P Cras.

At least 91 records · Page 5Linked to original sources
PubMed1991

Microglia are associated with the extracellular neurofibrillary tangles of Alzheimer disease.

When neurons die, the filaments of neurofibrillary tangles (NFT) undergo structural and antigenic modifications. The exact mechanism of this modification is unknown, but glial cells could play an important role. Previous studies have shown that astroglial processes infiltrate extracellular NFT. In this study we use double immunolabelling to show that microglia also infiltrate extracellular NFT. Therefore, along with the previously identified astroglia, the microglia could be responsible for the modification of extracellular NFT.

Aged↗
PubMed1991

Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

Senile plaques are polymorphous beta-amyloid protein deposits found in the brain in Alzheimer disease and normal aging. This beta-amyloid protein is derived from a larger precursor molecule of which neurons are the principal producers in brain. We found that amyloid precursor protein (APP)-immunoreactive neurites were involved in senile plaques and that only a subset of these neurites showed markers for the abnormal filaments characteristic of neurofibrillary pathology. In the neocortex of nondemented individuals with senile plaques but spared of neurofibrillary pathology, dystrophic neurites in senile plaques showed only APP accumulation. In contrast, in the brains of Alzheimer patients, virtually all APP-immunoreactive neurites also showed immunoreactivity with ubiquitin, tau, and phosphorylated neurofilaments. The presence of tau and neurofilament epitopes in dystrophic neurites in senile plaques was correlated with the extent of neurofibrillary pathology in the surrounding brain tissue. Accumulation of APP and the formation of neurofibrillary pathology in senile plaque neurites are therefore distinct phenomena. Our findings suggest that APP accumulation in senile plaque neurites occurs prior to tau accumulation and is therefore more closely related to appearance of neuritic dystrophy.

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

Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease.

Neurofibrillary tangles (NFT) are abnormal filamentous inclusions that develop in neurons in Alzheimer disease and other disorders. When neurons die, the neurofibrillary tangles that persist in the extracellular space show ultrastructural and antigenic changes. Both intra- and extracellular NFT have recently been shown to contain heparan sulfate proteoglycans (HSPGs). HSPGs are also present in other amyloid deposits in the brain and in systemic amyloidoses. Basic fibroblast growth factor (bFGF) is a heparin binding growth factor which is involved in angiogenesis and also has neurite promoting activity. We now report that bFGF binds avidly to extracellular NFT. Alz-50, a monoclonal antibody (MAb) to an abnormal form of tau and bFGF binding label mutually exclusive subpopulations of neurofibrillary tangles. bFGF binding is abolished by heparinase or heparitinase treatment and therefore is most likely based on the presence of HSPG. Binding of bFGF is a specific and sensitive morphological method to distinguish intra- from extracellular NFT. As intracellular NFT, which also contain HSPGs, are not labeled by bFGF binding, this finding also suggests that HSPGs are modified when the NFT become extracellular.

Aged↗
PubMed1991

Early-onset Alzheimer's disease in 2 large Belgian families.

Familial Alzheimer's disease (FAD) is a dominantly inherited condition that may present with an early onset, and myoclonus occurs frequently in the course of the disease. We report clinical and neuropathologic data on 2 large Belgian families with FAD in which we obtained 17 autopsies of the CNS. In family A, each of 11 autopsies had the typical neuropathologic features of Alzheimer's disease (AD), and there were a few cerebellar plaques in the molecular layer. In family B, in addition to the typical characteristics of AD in 6 autopsies, there were numerous amyloid plaques in the cortical cerebellar layers. In both families, we immunostained the amyloid deposits for the A4 protein, and they were negative for prion-associated protein immunoreactivity.

Adult↗
PubMed1991

Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's disease.

The major intracytoplasmic lesion of Alzheimer's disease is the neurofibrillary tangle (NFT), which is primarily composed of paired helical filaments (PHFs). The mechanism responsible for the formation of PHFs, as well as their insolubility and apparent heterogeneity, is unknown. We found that basic fibroblast growth factor (bFGF) binds to heparinase-sensitive sites in NFTs. bFGF binding is due to a heparan sulfate proteoglycan (HSPG) immunocytochemically identified in NFTs. In the presence of polycations (e.g., Ca2+), HSPG will bind to free carboxyl groups in NFT proteins. HSPG binding may play a role in transforming normal soluble proteins into insoluble PHFs.

Aged↗
PubMed1990

A monoclonal antibody raised against Alzheimer cortex that specifically recognizes a subpopulation of microglial cells.

A monoclonal antibody (MAb), termed AMC30, was raised after in vitro immunization with sonicated neurofibrillary tangle (NFT)-enriched fractions prepared from Alzheimer's brain. The antigen to which AMC30 is directed was expressed by microglial cells in senile plaques of Alzheimer's disease (AD). Microglia in the parenchyma surrounding brain tumors or infarctions, multinuclear giant cells, perivascular and parenchymal macrophages throughout the brain of AIDS patients were also labeled. Different non-nervous system lesions in which macrophages participate were also stained. Microglial cells in normal areas of the cortex or white matter were not labeled with MAb AMC30. The antigen to which AMC30 is directed was not detected in normal bone marrow, lymph nodes, lung, or spleen monocytes or macrophages. The epitope recognized by MAb AMC30 was present after formalin fixation and paraffin embedding. Our findings suggest that this MAb is directed against an antigen that is specifically expressed in a subpopulation of microglial cells and macrophages reactive to various pathological conditions.

AIDS Dementia Complex↗
PubMed1990

Neuronal and microglial involvement in beta-amyloid protein deposition in Alzheimer's disease.

This study was undertaken to localize amyloid precursor protein (APP) and to determine how APP might be released and proteolyzed to yield the beta-amyloid protein deposits found in senile plaques in the brains of Alzheimer's disease patients. We found that antibodies to recombinantly expressed APP labeled many normal neurons and neurites. In addition, dystrophic neurites in different types of senile plaques and degenerating neurons in the temporal cortex and hippocampus of Alzheimer's disease patients were immunostained. We also detected small clusters of dystrophic APP immunoreactive neurites that were not associated with beta-amyloid protein deposits. Microglia was involved in different types of senile plaques and often were associated closely with APP immunoreactive neurites and neurons. The greatest concurrence of APP immunoreactivity and reactive microglia was seen in the subiculum and area CA1, regions with a high density of congophilic plaques and subject to intense Alzheimer's pathology. Our findings suggest that neuronally derived APP is the source for senile plaque beta-amyloid protein, while microglia may act as processing cells.

Aged↗
PubMed1988

Gamma-enolase and glial fibrillary acidic protein in nervous system tumors. An immunohistochemical study using specific monoclonal antibodies.

A large series of central and peripheral nervous system tumors was studied for the presence of glial fibrillary acidic protein (GFAP) and gamma-enolase (neuron-specific enolase, NSE), using specific monoclonal antibodies (mAbs). Occurrence in and specificity of GFAP to glial and mixed tumors was confirmed and depended on the malignancy grade and features such as meningeal invasion. Using a well-characterized mAb, gamma-enolase was demonstrated in neuronal, as well as in a whole range of non-neuronal tumors. This lack of specificity of gamma-enolase prohibits its use as an exclusive neuronal marker. Nevertheless quantization or comparison with other types of enolases could still prove to be useful in well-defined situations. The advantages inherent to mAbs and a highly sensitive detection system turn GFAP stainings into a specific and readily reproducible technique.

Antibodies, Monoclonal↗
PubMed1987

Immunohistochemical localization of S-100 protein, glial fibrillary acidic protein, and neuron-specific enolase in the pars distalis of quail, rat, and human hypophyses.

In the present study, we have localized immunohistochemically S-100 protein, glial fibrillary acidic (GFA) protein, and neuron-specific enolase (NSE) by the unlabelled antibody peroxidase-antiperoxidase technique. Special attention was paid to the influence of fixation and of pretreatment of sections with proteolytic enzymes. It appeared that the final immunostaining of a given antigen largely depends on the fixative and on the species used. Moreover, pepsin pretreatment proved to be necessary to unmask S-100 protein in quail and GFA protein in rat. S-100 protein (rat, human) and GFA protein (human) immunoreactivities were detected in the folliculo-stellate (FS) cells. In quail, S-100 protein was also found in cells, which were not arranged around a follicular lumen and, in rat, the endothelial cells were immunostained for GFA protein. Clusters of granular cells were weakly immunostained for NSE in all species. An exclusive relationship between FS cells and S-100 protein could not be ascertained from this study.

Animals↗
PubMed1987

Spinal neuroaxonal dystrophy and angioneuromatosis.

A man of 75 years of age had had lightning pains in the legs for 8 years. Clinical examination demonstrated mild pyramidal signs and involvement of the posterior columns. A morphine pump was placed in the epidural space in the lumbar region to treat the pain. He died two weeks later from a massive pulmonary embolism. The nervous system was examined using the classical techniques along with the use of poly- and monoclonal antibodies against nervous system specific proteins. The following features were demonstrated: neuroaxonal dystrophy of the posterior and anterior horns, and the posterior columns and corticospinal pathways in decreasing order of importance; angioneuromatosis of the grey matter of the lumbosacral spinal cord and loss of neurons of the dorsal spinal root ganglia and bilateral degeneration of the fasciculus gracilis. Previously, we have only found such amounts of spheroids in the spinal cord as measured here in cases of Seitelberger's disease. The angioneuromatosis was isolated and did not result from previous trauma nor was it associated with a known phacomatosis. This combination of features is very unusual and may explain the clinical features including the lightning pains.

Aged↗
PubMed1987

Distribution of biogenic amines and their catabolites in brains from patients with Alzheimer's disease.

Norepinephrine, epinephrine, dopamine, serotonin and their major catabolites were measured in 17 regions of the left hemisphere of two brains obtained from two brothers with Alzheimer's disease with very early onset. The clinical diagnosis was confirmed by histological examination of the right hemispheres and brain stems. The quantitative data were compared with our values in normal brains. In the patient suffering from the less severe dementia, there was a severe reduction of the serotonin concentration in all examined neocortical areas and its concentration was even below the detection limit in the nucleus amygdalis, hippocampus, caudate nucleus, putamen, globus pallidus and substantia nigra. In the other patient, who suffered from a more pronounced dementia with myoclonus, the serotonin concentration was below the detection limit in all examined structures. In contrast with these findings, the noradrenergic, adrenergic and dopaminergic systems appeared to be relatively unaffected by the disease process. Focusing our attention on the nuclei wherein the monoamine transmitter systems originate, it appeared that neuronal losses and neurofibrillary tangles clearly predominated in the substantia grisea subependymalis, the nucleus centralis superior and the nucleus raphe dorsalis, origin of the main serotonergic system. The serotonin deficiency sheds light on possible mechanisms of myoclonus in Alzheimer's disease.

Adult↗
PubMed1987

Hamartoma of the tuber cinereum in a six-month-old boy, causing isosexual precocious puberty.

A case of hamartoma of the tuber cinereum causing isosexual precocious puberty in a six-month-old boy, in whom the lesion was successfully extirpated, is presented. Our patient was relatively young, since hamartomas causing sexual precocity most often occur between the ages of one and three years. Hamartomas are discussed from the clinical and pathological points of view. The mechanisms of initiating pubertas praecox in cases of cerebral tumours, particularly hamartomas, are reviewed.

Hamartoma↗
PubMed1987

Human gamma gamma-enolase: two-site immunoradiometric assay with a single monoclonal antibody.

A monoclonal antibody (mAb), termed BBS/NC/VI-H14 (H14), that reacts with the human enzyme gamma gamma-enolase was prepared. It was directed against the gamma-subunit and did not cross-react with the alpha- or beta-subunit. The mAb H14 can be used for quantitative determination of gamma gamma-enolase in a two-site immunoradiometric assay (two-site IRMA). It is also suitable for immunostaining formalin-fixed tissues. The specific identification of gamma gamma-enolase provided by the two-site IRMA with H14 is discussed in relation to the cellular distribution of this protein.

Animals↗
PubMed1986

Guillain-Barré syndrome with ophthalmoplegia: clinicopathologic study of the central and peripheral nervous systems, including the oculomotor nerves.

The neuropathologic findings are described in a fatal case of Guillain-Barré syndrome with ophthalmoplegia. Demyelination was found in the oculomotor nerves, which were dissected to the terminal branches in the ocular muscles, and in other peripheral nerves. The CNS was intact except for occasional chromatolytic lesions in some motor nerves.

Brain↗