Biomedical subjects

C Bancher

Publications and source records attributed to C Bancher.

49 records · Page 3Linked to original sources

PubMed1990

Alzheimer neuropathology in non-Down's syndrome mentally retarded adults.

We examined the brains of 385 mentally retarded adults aged 23-90 years without Down's syndrome (DS), metabolic disorder, or hydrocephalus to extend our knowledge about the occurrence of Alzheimer-type neuropathology in this population. Relevant measures of neuropathology also were related to selected information available from clinical records. The presence of one or more neurofibrillary tangles (NFT) and/or neuritic plaques (NP) was observed in 63.4% of all cases and varied with age. The prevalence of positive cases was higher when mental retardation was due to head trauma, congenital malformation, or familial factors and when a history of seizures was reported. Comprehensive morphometric analyses of neocortical, hippocampal and parahippocampal areas indicated that recommended age-specific quantitative criteria for the diagnosis of Alzheimer disease [Khachaturian ZS (1985) Arch Neurol 42:1097-1105] were met in 9.5% of cases less than 50 years of age, 54.2% between 50 and 65, 70% between 66 and 75, and 87% of the cases greater than 75 years of age. However, a limited immunohistochemical study revealed that in most cases the NP did not have a neuritic component containing paired helical filaments and in this respect most of the plaques observed in this population may differ from those most strongly associated with Alzheimer disease. In addition, substantial numbers of NFT were seen in frontal cortex, contrasting with results reported in the literature for nonretarded populations. The number of NP per mm2 consistently increased with age for all areas examined, while the relationship between NFT density and age varied across areas, and was clearly not monotonic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease.

The intraneuronal accumulation of paired helical filaments in the form of neurofibrillary tangles is one hallmark of the brain pathology in Alzheimer's disease. At certain predilection sites, a small number of similar lesions are also present in the brains of the majority of aged non-demented individuals. As suggested by several studies before, these abnormal cytoskeletal structures contain determinants of microtubule-associated protein tau and ubiquitin. The present study uses a morphological classification of neurofibrillary tangles into different stages of maturation, as suggested by Alzheimer in 1911, and shows by quantitative immunocytochemistry that early stages of neurofibrillary degeneration contain abnormally phosphorylated tau. Immunoreactivity for the altered tau is seen not only in tangles but also in the cytoplasm of some nerve cells lacking neurofibrillary tangles. Similar numbers of such immunoreactive neurons without tangles are present in age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls. In contrast, incorporation of an epitope, recognized by a monoclonal antibody (3-39) raised to paired helical filaments, which is directed against a determinant residing in the 50-65 amino acid residue region of ubiquitin occurs late in the process of tangle maturation and is most pronounced in extracellular 'ghost tangles'. It is suggested that the accumulation of abnormally phosphorylated tau is one of the earliest cytoskeletal changes in the process of tangle formation. Exposure of certain ubiquitin epitopes in the pathological fibers may reflect an unsuccessful attempt of proteolytic degradation.

Adult↗

PubMed1989

About the presence of paired helical filaments in dystrophic neurites participating in the plaque formation.

Immunocytochemistry with monoclonal antibodies to the beta-protein and to antigens associated with paired helical filaments (PHF) allows us to selectively stain two major components of neuritic (senile) plaques (NP): PHF and amyloid deposits. Using this method, the structure of NP in the brains of Alzheimer disease victims was compared to their structure in the brains of non-demented aged individuals selected for high numbers of NP. It is demonstrated that the dystrophic neurites participating in the plaque formation contain PHF only when cortical nerve cells in the same brain area form neurofibrillary tangles (NFT). People with many NP and many NFT were always demented, whereas people with many NP but few, if any NFT were not. It is speculated that there is individual susceptibility to the formation of PHF and that their appearance may represent a nonspecific response of the neuronal network to different kinds of injuries, like the deposition of amyloid in Alzheimer disease, or other pathogenic factors associated with various dementive neurodegenerative diseases. It is hypothesized that the deposition of brain amyloid in people resistant to neurofibrillary pathology may induce too little dysfunction for the development of dementia.

Aged↗

PubMed1989

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease.

Immunocytochemical staining with monoclonal antibodies to the beta-protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the beta-protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word "plaques" does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto- and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.

Aged↗

PubMed1989

An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination.

An antigenic profile of subcortical and cortical Lewy bodies was determined in the presence or absence of neurofibrillary tangles in the same brain using antisera and monoclonal antibodies to various cytoskeletal elements as well as to determinants not present in the normal cytoskeleton. The cores of many Lewy bodies were strongly reactive with a monoclonal antibody to paired helical filaments which has been shown to recognize ubiquitin. This antibody also stained Marinesco bodies in the same tissue sections. Two monoclonal antibodies to phosphorylated epitopes of neurofilament proteins (SM I 31, SM I 34) stained the peripheries of about 40% of all discernable Lewy bodies on untreated paraffin sections. Reactivity with a monoclonal antibody to neurofilaments (SM I 33) appeared only after pretreatment of the sections with phosphatase. Lewy bodies did not bind antibodies to tau protein. Our results show that, as previously shown for neurofibrillary tangles, Lewy bodies also contain ubiquitin. The uncovering of neurofilament epitopes by treatment with phosphatase indicates that abnormal phosphorylation of cytoskeletal elements may play a role in the pathogenesis of the Lewy body.

Aged↗

PubMed1989

Tau and ubiquitin immunoreactivity at different stages of formation of Alzheimer neurofibrillary tangles.

In his original 1911 publication Alois Alzheimer classified neurofibrillary tangles (ANT) into three morphologically defined subgroups according to their stage of maturation. The present study shows that changes in the morphological appearance of ANT during their maturation process are accompanied by changes in their antigenic profile. As shown by several immunocytochemical studies these abnormal phosphorylated microtubule-associated protein tau and of ubiquitin. In this study, immunoreactivity for the altered tau is not only seen in a subset of tangles but also in the cytoplasm of some nerve cells lacking ANT, which we believe to be at a stage of neuronal alteration preceding the formation of compact tangles (Stage 0 tangles). Similar numbers of Stage 0 tangles are present in the brains of age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls lacking ANT. In extracellular "ghost tangles", the ultimate stage of neurofibrillary degeneration, immunoreactivity for tau is accessible to antibodies only when tissue sections are pretreated with formic acid to uncover the binding sites. In contrast to tau, presence/accessibility of an epitope residing on residues 50-65 of ubiquitin recognized by a monoclonal antibody raised to paired helical filaments (3-39) increases during the maturation of ANT and is most pronounced in "ghost tangles". Appearance/uncovering of the 3-39 epitope and masking of tau reactivity during tangle maturation may reflect degradation or conformational changes in the pathological filaments due to their aging and the final loss of their parent nerve cells.

Aged↗

PubMed1989

A 31 kilodalton beta-protein immunoreactive polypeptide in neuronal lipofuscin.

The beta-protein, a small fibrillar peptide which is the main constituent of the amyloid deposits in senile neuritic plaques and congophilic angiopathy derives by proteolytic cleavage from at least one of three large precursor proteins of 695 to 770 amino acids encoded by a gene on chromosome 21. In the brain the mRNA coding for these predicted proteins has been localized to neurons and non-neuronal cell types. Monoclonal antibodies raised to a synthetic peptide corresponding to residues 1 to 24 of the beta-protein do not only stain the amyloid deposits characteristic for Alzheimer neuropathology, but also neuronal lipofuscin. This material is immunoreactive in every brain area examined (cerebral and cerebellar cortices, basal ganglia, brainstem) and its reactivity is independent from the presence of Alzheimer's disease. At the ultrastructural level immunoreactivity is associated with the proteinaceous matrix part of lipofuscin which does not contain any fibrillar structures. Western blotting of a lipofuscin enriched fraction shows a beta-protein immunoreactive polypeptide migrating at approximately 31 kDa position on SDS-polyacrylamide gel electrophoresis. These results suggest that a large fragment of the amyloid precursor protein (approximately 280 residues) is associated with lipofuscin. Unlike in the microglial cell where the amyloid precursor is processed in a manner to release the beta-protein which forms amyloid fibers, one pathway of its physiological breakdown in the nerve cell seems to yield a large fragment which accumulates on a lipopigment characteristic for normal aging.

Aged↗

PubMed1987

Neurofibrillary tangles in Alzheimer's disease and progressive supranuclear palsy: antigenic similarities and differences. Microtubule-associated protein tau antigenicity is prominent in all types of tangles.

The antigenic profile of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT), progressive supranuclear palsy (PSP) and in non-demented aged humans was investigated by light and electron microscopic immunocytochemistry using antisera and monoclonal antibodies to tubulin, microtubule-associated proteins (MAP1, MAP2 and tau), neurofilament proteins and determinants unique to Alzheimer paired helical filaments (PHF). Antibodies to tau proteins labeled NFT in all cases investigated (AD, SDAT, PSP and non-demented aged humans). However, one monoclonal antibody to PHF recognized numerous tangles in AD/SDAT, but only a small minority of the PSP tangles. Antibodies to tubulin, MAP1, MAP2 and neurofilament proteins did not selectively stain NFT. Whereas pretreatment of sections with phosphatase was required for the detection of tangles with Tau-1 monoclonal antibody, digestion of sections with either phosphatase or pronase had no significant effect on the staining pattern obtained with the other antibodies. Our studies show that, as previously described for AD/SDAT, phosphorylated tau polypeptides are also a major antigenic determinant of tangles in PSP, indicating that tangle formation may follow a common pathogenetic pathway in neurofibrillary degenerations. There is, however, at least one epitope in AD/SDAT tangles which seems to be absent on, or at least inaccessible in, the 15-nm straight fibrils of PSP.

Adult↗

PubMedDate not supplied

Immunoreactivity of neuronal lipofuscin with monoclonal antibodies to the amyloid beta-protein.

Monoclonal antibodies generated against a synthetic peptide corresponding to amino acids 1 to 24 of cerebrovascular amyloid beta-protein do not only stain amyloidotic blood vessels and the amyloid deposits of the (senile) neuritic plaques, but also the neuronal pigment lipofuscin. Staining of lipofuscin is observed in both cerebral and cerebellar cortices, subcortical nuclei as well as the brain stem, and is identical in Alzheimer and normal control brain. Western blots of a lipofuscin enriched fraction show an anti-beta-protein reactive polypeptide migrating at approximately 31 kDa position on SDS-polyacrylamide gel electrophoresis. These results suggest that this polypeptide is associated with lipofuscin and is most likely derived from the predicted amyloid precursor protein. This implicates that, unlike in Alzheimer's disease where this protein is also processed extraneuronally in a manner to release an amyloid fiber forming fragment, the end point of its processing in the nerve cell seems to accumulate on a lipopigment characteristic for normal aging.

Adolescent↗

PubMedDate not supplied

Cytoskeletal protein pathology and the formation of beta-amyloid fibers in Alzheimer's disease.

Discovery of the abnormally phosphorylated tau in paired helical filaments, its accumulation preceding the formation of the tangles and the in vitro microtubule assembly defect suggest that an abnormality in the protein phosphorylation/dephosphorylation system is involved in the pathogenesis of Alzheimer cytoskeletal pathology. The levels of mRNA for the beta-amyloid precursor protein (beta APP) in the brain suggest that only a small deficiency in the processing of the precursor would be sufficient to account for the accumulation of beta-amyloid in Alzheimer brain. Identification of reticuloendothelial system cells responsible for the production/processing of beta-amyloid will help to elucidate the pathogenesis of the brain amyloidosis. The disproportionate accumulation of paired helical filaments and amyloid within the same affected brain and from disease to disease raises the possibility of different etiologies for each of these lesions coexisting in Alzheimer's disease.

Alzheimer Disease↗

PubMedDate not supplied

On the relationship between measles virus and Alzheimer neurofibrillary tangles in subacute sclerosing panencephalitis.

We have studied the relationship between measles virus and the accumulation of abnormally phosphorylated tau (PHF-tau) in nine cases of subacute sclerosing panencephalitis (SSPE). By assessing the presence of viral intranuclear inclusions and neurofibrillary tangles (NFT) in each case, we found no correlation between presence and amount of measles virus and the numbers of neurons containing PHF-tau. Immunohistochemical double labeling in a case with long duration of disease and severe histopathologic change revealed no strict colocalization of measles virus antigen and PHF-tau throughout different brain regions. In areas containing both antigens, most neurons carrying measles virus did not have a tangle and vice versa, eventhough some colocalization beyond that expected by chance was observed in specific cortical areas. These results indicate that, although secondary to viral infection, NFT formation in SSPE is not restricted to cells carrying viral antigen. Conversely, measles virus infected cells do not necessarily accumulate PHF-tau. This lack of colocalization at the cellular level, throughout different brain areas and among different cases suggests that the formation of NFT in SSPE is not directly induced by the infectious agent. The formation of NFT in this disease appears to be elicited through a specific type of tissue damage and, thus, to be an epiphenomenon. This pathogenetic detail may be of interest for our understanding of the role of neurofibrillary degeneration in the pathogenesis of other more frequent neurodegenerative diseases with cytoskeletal pathology.

Adolescent↗

PubMedDate not supplied

Proposals for re-evaluation of current autopsy criteria for the diagnosis of Alzheimer's disease.

Defining criteria for the postmortem diagnosis of Alzheimer's disease (AD) has proven difficult due to the phenotypical heterogeneity of the disease, the absence of a specific disease marker and an overlap of AD neuropathology with that observed in a number of nondemented aged individuals. Even though the role of plaques and tangles in the pathogenesis of AD remains undetermined, a host of clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers-particularly in the neocortex-are still to be considered the best morphological signposts for the disease. All currently used criteria for the neuropathologic diagnosis of AD have some weaknesses and need to be reestablished and revalidated. Multivariant analysis in a personal autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging of neuritic Alzheimer-type lesions, and less concordance with the National Institutes of Aging and Tierney criteria. We propose a set of histopathologic diagnostic criteria for both definite and preclinical AD that rely on various constellations of both different types of plaques, except diffuse amyloid deposits, and neurofibrillary tangles, in allocortical and isocortical areas considering their topographic pattern. This set of criteria encompasses phenotypic variations of the pathology and takes into account the chronic, progressive course of AD. It allows the detection of preclinical disease in subjects in whom dementia is not reported and includes those cases in the morphological gray zone between "normal" aging and full-fledged AD that practicing neuropathologists consider the most problematic. The set of criteria includes guidelines concerning tissue sampling and processing, and standardized staining methods that should allow neurologists to minimize interrater and interlaboratory variability in the assessment of morphologic lesions and the diagnosis of AD.

Aged↗

PubMedDate not supplied

[Histopathologic studies in dementia--comparison with clinical findings].

This paper compares the clinical diagnosis of dementia with the result of the neuropathological brain examination in 23 patients. Aim of this investigation was a verification of the clinical diagnosis. The diagnosis was based on the clinical findings, the Mini Mental State Examination, DSM-III-R classification of dementia, the NINCDS-ADRDA-criteria, results of laboratory tests, EEG, CCT and sonography. A total of 70% of the clinical diagnosis corresponded to the neuropathological results. In 25% of these cases which clinically showed the characteristics of Alzheimer's disease histopathological findings delineated dementia of non-Alzheimer-type. These results underline the importance of additional histopathological investigations in the diagnosis of dementia.

Aged↗