PubMed Health⌕ Search

Biomedical subjects

A Defossez

Publications and source records attributed to A Defossez.

33 records · Page 2Linked to original sources
PubMed1989

Alzheimer's disease: glycolytic pretreatment dramatically enhances immunolabeling of senile plaques and cerebrovascular amyloid substance.

In Alzheimer's disease, three types of pathologic lesions are stained by thioflavin: neurofibrillary tangles, senile plaques, and amyloidaceous vessels. We have used anti-beta protein amyloid A4 and anti-tau protein antisera and compared immunolabeling with thioflavin staining. Anti-tau detected only neurofibrillary tangles; anti-beta-PA4 immunostained senile plaques and amyloidaceous vessels. Glycolytic pretreatment (2% periodic acid overnight or glycosidases digestion) dramatically enhanced the anti-beta-PA4 immunolabeling of senile plaques, amyloidaceous vessels, and a previously undetected extracellular substance; neurofibrillary tangles were never immunostained. Therefore, glycolytic pretreatment exposes buried epitopes in the amyloid and is a good method for amplification of immunostaining. The nature of the interaction between saccharides and beta-protein amyloid A4 is unknown.

Alzheimer Disease↗
PubMed1989

[Direct demonstration of abnormal phosphorylation of Tau microtubular proteins in Alzheimer's disease].

Two polyclonal antibodies, the first raised against Alzheimer's disease PHF and the second raised against human native Tau proteins, led us to find two Tau proteins with an abnormal molecular weight of 64 and 69 kDa in Alzheimer brain cortices. Tau 64 and Tau 69 were never detected in control brains. The molecular weight of Tau 64 and 69 dramatically decreased after dephosphorylation by the alkaline phosphatase, showing that they are abnormally phosphorylated. This is the first report demonstrating their specific presence in brain regions having the Alzheimer pathology. They could be a very useful tool for the study of the early events that lead to neuronal death.

Alkaline Phosphatase↗
PubMed1989

[Alzheimer's disease: immunohistochemical characterization of cerebral amyloid deposits].

In Alzheimer cortex tissue sections, thioflavine stained three patterns of amyloid lesions: neurofibrillary tangles (NFT), senile plaques (SP) and vessel walls (amyloid angiopathy AA). An anti serum against Tau proteins detected NFT but neither SP nor AA. In contrast, an anti serum against beta protein amyloid (BP A4) revealed SP and AA but not NFT. A periodic acid pretreatment dramatically enhanced the anti-BP A4 immunolabelling corresponding to microplaques as well as a large amount of diffuse extracellular amyloid substance, but never stained NFT. Pretreatment of tissue sections with a mixture of endo and exoglycosidases gave identical results and corroborates the extraneuronal processing of BP A4 that appears in a glycosylated form in the extracellular compartment.

Alzheimer Disease↗
PubMed1988

Preferential localization of copper zinc superoxide dismutase in the vulnerable cortical neurons in Alzheimer's disease.

The distribution of cells containing CuZn superoxide dismutase (CuZn SOD) was determined in hippocampi and associative cortex from normal and Alzheimer's individuals by using antisera against native and denatured CuZn SOD proteins. Immunostaining was intense in large pyramidal neurons, moderate in hippocampal granule cells and very weak in other cells. In the hippocampus of an Alzheimer's patient, successive immunostaining of the same tissue section by anti CuZn SOD and anti paired helical filaments antisera show that both normal and degenerating cells are labelled by the anti CuZn SOD antiserum. Thus, large pyramidal neurons which are potentially susceptible to degenerative processes in AD have the property to contain higher amounts of CuZn SOD than other brain cells.

Aged↗
PubMed1988

Alzheimer's disease: a new evidence for common epitopes between microtubule associated protein Tau and paired helical filaments (PHF): demonstration at the electron microscope level by a double immunogold labelling.

Paired helical filaments (PHF) are neuronal landmarks of Alzheimer's disease. These pathological filaments are antigenically related to proteins present in the normal cytoskeleton, particularly to microtubule associated protein Tau. The evidence for these common epitopes was studied on sections of cortex from Alzheimer brains after Araldite embedding. Two rabbit immune sera were used: one was raised against PHF isolated from Alzheimer cortex; the other against Tau proteins extracted from bovine cortex. The comparison of adjacent semi-thin sections alternatively treated with anti-PHF and anti-Tau immune sera reveals that both stained degenerating neurofibrils in pyramidal perikarya and in neurites surrounding senile plaques. On ultra-thin sections, double immunogold labelling of PHF was obtained. These results are in accordance with the hypothesis that Tau proteins are major antigenic components of PHF.

Alzheimer Disease↗
PubMed1987

Observation of morphological relationships between angiopathic blood vessels and degenerative neurites in Alzheimer's disease.

Two main techniques are used to stain the three types of brain lesions characteristic of Alzheimer's disease: Neurofibrillary tangles (NFT), senile plaques (SP) and congophilic angiopathy. Thioflavine-S is an histochemical marker of the amyloid substance located essentially in the central core of senile plaques and in the walls of the pathological blood vessels. Specific antibodies against Paired Helical Filaments (PHF), the ultrastructural elements of NFT, reveal neuron cell bodies with NFT and numerous dystrophic neurites, mostly around neuritic plaques. Using simultaneous histochemical and immunohistochemical labellings on the same tissue sections of Alzheimer cortex (association cortex and hippocampus), the different lesions were stained with great sensitivity and specificity. Moreover, an unusual morphological relationship between two types of lesions was detected in two Alzheimer brains with prominent congophilic angiopathy: we observed a well marked concentration of dystrophic neurites, immunolabelled with anti-PHF, around blood vessels with Thioflavine-S stained amyloid angiopathy. These lesions were distributed like a sleeve around 1/10 of dyshoric or congophilic blood vessels. The significance of such lesions is unknown but they probably represent a step of the pathogenesis of Alzheimer brain lesions and may explain the general mechanism of lesion formation in Alzheimer's disease.

Aged↗
PubMed1987

[Immunocytochemical study at the ultrastructural level of neurofibrillary degeneration in Alzheimer's disease].

Paired Helical Filaments (PHF), as demonstrated at the ultrastructure level, are one of the main pathological landmarks of Alzheimer's disease (AD). A polyclonal rabbit antiserum raised against PHF had been shown to label tangles and the periphery of plaques at the light microscope level. The same antiserum labels PHF specifically at the ultrastructure level, as demonstrated with a postembedding immunogold technique. Normal cytoskeleton constituents and plaque amyloid were not labelled. Specific labelling of a characteristic landmark may be a clue for a biological marker of AD.

Alzheimer Disease↗
PubMed1986

Alzheimer's disease: Tau proteins, the promoting factors of microtubule assembly, are major components of paired helical filaments.

A rabbit antiserum was raised against paired helical filaments (PHF). This antiserum stains specifically neurofibrillary tangles (NFT) at the light-microscopic level and PHF at the electron-microscopic level in sections of Alzheimer neocortex and hippocampus. We studied the nature of the antigens recognized by this antiserum by immunocytochemistry, immunoblots and immunoadsorption. These approaches showed that the anti-PHF specifically labels a set of low molecular weight 65-50 kDa microtubule-associated proteins, named Tau proteins, which are promoting factors of microtubule assembly. Furthermore, antisera against Tau proteins stained NFT. It is concluded that neurofibrillary tangles are very likely composed of aggregated Tau proteins. This process might be due to an abnormal Tau protein synthesis or to an unknown lesion of certain pyramidal neurons leading to an aggregation of Tau proteins.

Adult↗
PubMed1986

Biochemical and immunological studies of bovine and porcine neurofilament triplet proteins by peptide mapping after cyanogen bromide cleavage.

Peptide mapping of the three bovine and porcine neurofilament protein subunits ("L", "M" and "H") with apparent mol. wts of 70, 160 and 210 kDa were performed with CNBr, leading to the cleavage of methionyl bonds. We have obtained two characteristic large fragments with molecular weights of 85 kDa for the "M" bovine subunit and 135 kDa for the "H" subunit of bovine neurofilament. A comparison of the electrophoretic patterns of CNBr generated polypeptides of "L" subunit from beef and pig showed that they are highly related structures. The peptide mappings of CNBr peptides of "M" and "H" subunits from beef and pig were significantly different. Antibodies were raised against the 85 kDa and 135 kDa CNBr fragments. Immunoblotting results with anti-85 kDa and anti-135 kDa of beef are in favour of large differences of structure between the "M" subunits from pig and beef. The "H" proteins were very similar and they also showed that the C-terminal part of bovine "H" and "M" proteins share common antigenic determinants.

Animals↗
PubMed1985

Anti-PHF antibodies: an immunohistochemical marker of the lesions of the Alzheimer's disease. Characterization and comparison with Bodian's silver impregnation.

An immune serum raised against paired helical filaments (PHF) was able to stain senils plaques (SP) and neurofibrillary tangles (NFT) specifically, the two characteristic lesions of the dementia of Alzheimer-type. This polyclonal antibody against PHF was characterized by immunochemistry and also compared with the classical Bodian silver staining. NFT and SP were observed where they were expected: in the fronto-temporal neo-cortex and hippocampus of Alzheimer-type patients, and also in hippocampus of non-demented elderly subjects. The pattern of SP visualized by the two methods was identical whereas NFT were not detected specifically by silver salts, specially in the nervous tissue where NFT were in discrete quantities. Since the preparation of the antigen is very easy and the resulting antibodies are specific, we conclude that this technique will be of considerable interest for routine neuropathological diagnosis. Finally, the properties of our anti-PHF antibody are compared with those reported in the literature. This antibody will probably be a good tool for the identification of the chemical nature of PHF components.

Adult↗
PubMed1983

Gonadotrophin-like substance in the testis. Immunocytochemical localization in the guinea pig.

A gonadotrophin-like material (GLM) was observed by immunocytochemical methods in prepuberal guinea pig testes, not only on Sertoli and interstitial cells, but also on spermatogonia and spermatocytes. The intracellular cytoplasmic localization of GLM is discussed in relation to the receptor internalization theory. Variations between young and adult animals allowed us to approach the physiological significance of testicular GLM.

Animals↗
PubMedDate not supplied

Dystrophic neuropeptidergic neurites in senile plaques of Alzheimer's disease precede formation of paired helical filaments.

The relationship between peptidergic neurites and paired helical filaments (PHF)-positive neurites in Alzheimer's disease (AD) senile plaques (SP) was studied using combined fluorescence and bright field optics. Cryostat sections of AD hippocampi were first stained by thioflavine-S and immunolabeled with antisera raised against different neuropeptides: somatostatin 28(1-12) (som 28(1-12)), somatostatin 14 (som 14), neuropeptide Y (NPY), cholecystokinin (CCK) and substance P (sP). Secondly, using the elution-restaining procedure, sections were immunolabeled with anti-tau/PHF. In immature SP, clusters of abnormal, swollen neurites were found. The dystrophic, strongly peptidic-positive neurites contained less PHF than the poorly positive ones. Cell bodies, exhibiting a peptidic content, could be found within SP without any alteration. These results suggest the following sequence of events: an extracellular poisoning mechanism, perhaps the amyloid substance, first changes the structure of presynaptic endings and causes the formation of ballooning dystrophic neurites filled with their normal peptidic content. Subsequently, intracellular degradation occurs with formation of the PHF. Then the other structures such as dendrites and perikarya are damaged by the same mechanism. Therefore this phenomenon seems to precede any formation of PHF in SP.

Alzheimer Disease↗
PubMedDate not supplied

[Immunohistochemical study of the basic lesions of Alzheimer's disease].

Alzheimer's disease is characterized by the presence of two argentophilic histopathologic brain lesions: neurofibrillary tangles (NFT) and senile (neuritic) plaques (SP). NFT consist of large perikaryal masses of abnormal cytoplasmic fibers, most of which have the ultrastructural appearance of pairs of intermediate-sized (10 nm) filaments wound into a double helix and named Paired Helical Filaments (PHF). PHF also occur within the degenerating neurites of SP. The insolubility of PHF in strong detergents is turned to account for their isolation. We have isolated these structures from an Alzheimer brain and raised antibodies against PHF. The anti-PHF antibodies detected specifically NFT and SP on nervous tissue sections of Alzheimer brains, and also NFT in the hippocampus of normal aged brains. The stainings of NFT and SP by the anti-PHF or the classical Bodian silver staining technique were compared. The immunohistochemical method is more precise, more reproducible, more specific and will be of great interest for the quantification of these structures, specially when they are in minor quantities particularly in the atypical disease. Furthermore, the anti-PHF antibodies did not visualize neurofilament containing structures, and did not react with neurofilament protein subunits on immunoblots. These results are compared to those reported in the literature.

Adult↗