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A Delacourte

Publications and source records attributed to A Delacourte.

At least 145 records · Page 8Linked to original sources
PubMed1989

An antiserum to the N-terminal subsequence of the Alzheimer amyloid beta protein does not react with neurofibrillary tangles.

Polyclonal antibodies were raised against a synthetic peptide corresponding to a subsequence for the first 10 residues of the beta amyloid protein A4 (1-10 beta PA4). In an immunoperoxidase study of Alzheimer brain tissue, these antibodies immunostained senile plaque cores, amyloid vessel walls, and amyloid fibrils surrounding senile plaques and angiopathic vessels. Neurofibrillary tangles stained with thioflavin S or immunostained with anti-Tau immune serum were never immunodetected with the anti 1-10 beta PA4. We confirm that the neurofibrillary tangles do not contain epitopes corresponding to the first 10 residues of the beta PA4.

Alzheimer Disease↗
PubMed1989

Qualitative and quantitative comparison of brain proteins in Alzheimer's disease.

In human brain extracts, most proteins of pathological interest in Alzheimer's disease are insoluble and their analysis is often performed on denatured and reduced samples by immunoblotting after electrophoresis on polyacrylamide gel in presence of sodium dodecyl sulfate. Because we needed to accurately compare the concentration of several proteins in brain extracts to investigate the etiology of the disease, the quantitative aspect of immunoblotting was assessed and the results compared for a soluble component with those obtained by electroimmunoassay. Glial fibrillary acidic protein (GFAP) and Tau proteins were analysed by immunoblotting in brain homogenates treated with the Laemmli sample buffer from 10 control and 25 Alzheimer's disease brains. The linearity of densitometric measures of dilutions for one given sample was demonstrated. A 8 to 16-fold GFAP increase in Alzheimer brain was established. With regard to Tau proteins it was possible to show the presence of two pathological Tau variants (Tau 64 and 69) in all the Alzheimer brain homogenates, furthermore, the amount of Tau 64 and 69 was proportional to the presence of neurofibrillary degeneration. As far as alpha 1-antichymotrypsin is concerned, we showed, in a second set of brain samples (14 control and 12 Alzheimer brains), discrepancies between the results obtained by immunoblotting and by electroimmunoassay while for a given sample linearity of immunoblotting measures of dilutions of this sample was demonstrated. Quantitation by immunoblotting of such components which can be quantified using other procedures is uncertain whereas the interest of immunoblotting is undoubted for the insoluble proteins in the brain extracts.

Alzheimer Disease↗
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: the glial reaction is general and severe in all areas of the central nervous system].

GFAP (Glial Fibrillary Acidic protein) was quantified in unfractionated homogenates of different brain regions from 10 Alzheimer patients versus 25 controls using immunoblot techniques and anti-human GFAP. There was a strong increase of GFAP in the brain regions that contained the characteristic Alzheimer lesions. This corresponds to the "astrocytic gliosis". Moreover, there was a 11 fold GFAP increase (p less than 0.001) in the other regions of the Alzheimer brains that do not present the Alzheimer pathology, such as caudate nucleus, cerebellum or brain stem. Different from the gliosis, the physiological signification of such an increase in the whole brain is unknown, but it might reflect the prominent part played by astrocytes during Alzheimer's disease (AD).

Alzheimer Disease↗
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

Expression of ETS proto-oncogenes in astrocytes in human cortex.

In order to investigate a possible function of ETS proto-oncogenes in human brain, we incubated a polyclonal antibody raised against the viral region of E26 homologous to ETS1 and ETS2 with human brain frontal cortex sections. Our results show that this antibody decorates astrocytes but not neurons. By using astrocytomas of different grades as a source of astrocytes, we demonstrate the presence of ETS1 and ETS2 messenger RNAs and proteins. This leads to the idea that ETS genes are expressed in cells with dividing potentialities in human cortex and that they could provide a new marker for glial cells. Recently, a microduplication on chromosome 21 including ETS2 locus was described in karyotypically 'normal' Down's syndrome and suspected in Alzheimer's disease; when testing Alzheimer's disease-affected brain cortex sections, no obvious difference was observed with the technique used.

Antigens, Viral↗
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↗
PubMed1988

Cortical angiopathy in Alzheimer's disease: the formation of dystrophic perivascular neurites is related to the exudation of amyloid fibrils from the pathological vessels.

We studied the organization of dystrophic neurites around pathological vessels in Alzheimer cortex. Two techniques were used simultaneously on serial sections: thioflavine staining of amyloid substance and immunohistochemistry with immune sera against Paired Helical Filaments (anti-PHF) and native Tau proteins (anti-Tau). We observed different distributions of dystrophic neurites (immunolabelled with anti-PHF or anti-Tau) around thioflavine-stained angiopathic arterioles. The wall of the vessels with large diameter (greater than 100 microns) presented a congophilic angiopathy without neuropil reaction. In vessels with lesser diameter (less than 100 microns), dystrophic neurites constituted a discontinuous sleeve around vessels, always in close contact with amyloid substance outside the wall (dysphoric angiopathy). We observed structures similar to senile plaques around capillaries (diameter: 10-15 microns). The sleeve of dystrophic neurites with aggregated Tau proteins were always observed in the close vicinity of the amyloid substance which exuded from the pathological blood vessels. Thus, the exudation of these amyloid fibrils seems to induce the formation of dystrophic neurites (neuritic reaction).

Aged↗
PubMed1988

[Alzheimer's disease: study of the distribution of tau proteins constituting helical filament pairs in human central nervous tissue].

Tau proteins are the major components of Paired Helical Filaments (PHF) of Alzheimer's disease. Using the immunoblot technique and an antiserum against PHF, we have studied the distribution of Tau proteins in the different areas of normal human brains and Alzheimer brains. Tau proteins were clearly present in cortical grey matter but were difficult to detect in the white matter. In Alzheimer brains, we observed two differences: first, there is an important background due to the partial dissociation of the lesions containing Tau aggregates. Second, the profile of Tau proteins is modified, due to abnormal phosphorylation. Thus, Tau proteins are found in large amounts in the grey matter of the cortical areas and are not exclusively distributed in the axonal domain. The normal cortical distribution of Tau in the human brain correlates well with the distribution of histological lesions that contain PHF (neurofibrillary tangles and neuritic plaques) in the Alzheimer cortex.

Adult↗
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

Transformation of degenerating neurofibrils into amyloid substance in Alzheimer's disease: histochemical and immunohistochemical studies.

Degenerating neurofibrils (DNF), which are composed of paired helical filaments (PHF) and amyloid fibrils (AF), are the 2 characteristic pathological fibrillar deposits in Alzheimer cortex. These fibrils were simultaneously studied by 2 techniques: The immunolabelling with a specific antiserum raised against PHF and elective thioflavine S staining of AF. In neuronal perikaryons, neurofibrillary tangles (NFT) consist of 3 populations: firstly, strongly immunolabelled tangles were weakly thioflavine-stained. Secondly, less dense tangles were weakly immunolabelled but strongly thioflavine-stained. Thirdly, ghost tangles which correspond to extracellular NFT were exclusively thioflavine-stained. Thus, it is likely that NFT are degraded to form extracellular AF. Around neuritic plaques and some vessels with amyloid angiopathy, immunolabelled neurites, thioflavine-stained neurites and transition figures were also observed. On the other hand, the central core of plaques and pathological vessel walls were strongly thioflavine-stained but were never immunoreactive. In conclusion, these observations favour catabolism of PHF bundles found in NFT and in degenerating neurites into an amyloid substance. This amyloid substance seems different from other amyloid deposits found in the central core of neuritic plaques and vessel walls.

Aged↗
PubMed1987

Chemical modification of thiol group(s) in protein: application to the study of anti-microtubular drugs binding.

1. Different chemical procedures such as performic oxidation, carboxymethylation, carboxyethylation, aminoethylation, cyanylation, acylation, arylation etc. and addition of thiols to activated double bonds, titration of thiols with DTNB (Dithiobis-Nitro-Benzoate) and the reaction of thiols with organomercurials and the titration with p-chloro-mercuri-benzoate (PCMB) etc. are cited and discussed. Their chemical reactions are shown in the figures. 2. We describe in this paper that several chemicals interfere with microtubule assembly by combining with sulfhydryl residues. Reagents such as Cytochalasin-A and B, ethylacetylacrylate, FDNB (fluorodinitrobenzene), NEM (N-ethyl-maleimide), diamide, EBI (ethylene-bis-iodoacetamide, ethacrynic acid, methal ions, methylmercury, triethyllead ion and CDDP (cis-dichlorodiammine-platinum-II) are cited and their mechanisms are discussed.

Binding Sites↗
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

Applications of chemical cleavage procedures to the peptide mapping of neurofilament triplet protein bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

A procedure for examining possible sequence homology in the triplet neurofilament proteins using a sodium dodecyl sulfate-polyacrylamide gel electrophoresis system is described. Five different chemical reagents (cyanogen bromide, BNPS-skatole, hydroxylamine, formic acid, and nitrothiocyanobenzoic acid) have been used for peptide mapping studies. Potential applications of this technique are discussed.

Amino Acid Sequence↗
PubMed1986

Sequence homology analysis of proteins by chemical cleavages: using a mono and two dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

The examination of possible sequence homology in proteins using SDS-PAGE systems after chemical cleavage is described. After SDS-PAGE, the establishment of amino acid compositions, the techniques of staining gel and five different methods of chemical cleavages (cyanogen bromide, BNPS-skatole, hydroxylamine, formic acid and nitrothiocyano benzoic acid) have been used for peptide mapping studies. Potential applications of this technique are discussed from both the biochemical and immunochemical point of view.

Amino Acid Sequence↗