Biomedical subjects

C Bancher

Publications and source records attributed to C Bancher.

At least 19 recordsLinked to original sources

PubMed2003

Immunoreactivities of amyloid beta peptide((1-42)) and total tau protein in lumbar cerebrospinal fluid of patients with normal pressure hydrocephalus.

Immunoreactivities of amyloid beta peptide((1-42)) (Abeta42-IR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid of 48 patients (12 patients in each group) with normal pressure hydrocephalus (NPH), vascular dementia (VD), Alzheimer's disease (AD), Parkinson's disease without dementia (PD) and 24 controls (CON) using sensitive and specific enzyme immunoassays. TTIR in NPH was not significantly changed compared with VD, PD and CON, while NPH-Abeta42-IR was significantly decreased compared with PD and CON. In AD, significant increases of TTIR and significant decreases of Abeta42-IR were found. Using a TTIR by Abeta42 plot, all NPH, PD, and CON samples were within the non-AD plot region. 92% of AD and VD samples were within the AD and non-AD area, respectively. We conclude that combined measurement of Abeta42-IR and TTIR contributes to the differential diagnosis of NPH vs. AD and of AD vs. VD, respectively.

Adult↗

PubMed2000

Concurrence of sarcoidosis and aortitis: case report and review of the literature.

Takayasu arteritis (TA) is a rare manifestation of systemic large vessel vasculitis which affects predominantly the aorta and its main branches, but often remains unrecognised owing to delayed diagnosis and non-characteristic clinical features. Sarcoidosis, too, is a systemic inflammatory disease which can affect virtually any organ system. Reports about the coincidence of both diseases have appeared. The case presented here is characterised by a significant time lag between detection of TA and appearance of clinical signs of sarcoidosis. The woman, now 39 years old, had erythema nodosum, circumscript alopecia, and recurrent uveitis, which dated back to 1980 and was attributed to sarcoidosis. At least 12 years later aortic valve insufficiency with progressive cardiac failure developed. Histology performed at the time of aortic valve prosthesis in 1997 disclosed a diagnosis of TA, which was confined to the aortic root. Incidentally, sarcoidosis was diagnosed in adjacent lymph nodes. A thorough check up failed to detect further manifestations of TA; thus, possibly, the patients had aortitis similar to, but not identical with, TA. Several related cases previously reported are discussed, suggesting that both diseases may be inherently related as they are characterised by certain non-specific, immunoinflammatory abnormalities. This case report suggests that the prevalence of TA, or related forms of arteritis, may be higher than expected and should be considered, especially in younger patients with non-characteristic cardiovascular symptoms and suspected systemic inflammatory disease. Moreover, the association with sarcoidosis in this and other previously described cases suggests that the two diseases may be related and that TA or TA-like vasculitis may even be a complication of sarcoidosis.

Adult↗

PubMed1999

Giant visually-evoked potentials without myoclonus in the Heidenhain type of Creutzfeld-Jakob disease.

In a 64-year old woman with progressive visual impairment for 4 weeks, probable Creutzfeld-Jakob disease without myoclonus was diagnosed after rapidly progressive mental deterioration had also developed, and CSF and EEG showed characteristic findings. Pattern-reversal and flash visually-evoked potentials, recorded 5, 6, 7 and 8 weeks after onset, showed a maximum P100 latency of 210 ms, 8 weeks after onset, and a maximum N75/P100 amplitude of 33.1 microV, 5 weeks after onset. While the P100 latency progressively increased, the N75/P100 amplitude continuously decreased after reaching its maximum. In the Heidenhain type of Creutzfeld-Jakob disease giant visually-evoked potentials may be recorded during the early stages of the disease, even in the absence of myoclonus. Visually-evoked potentials may prove useful in diagnosing Creutzfeld-Jakob disease with atypical initial presentation.

Creutzfeldt-Jakob Syndrome↗

PubMed1999

Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF.

OBJECTIVE: To evaluate CSF levels of beta-amyloid(1-42) (Abeta42) alone and in combination with CSF tau for distinguishing AD from other conditions. METHODS: At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Abeta42 and tau. RESULTS: Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95% CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Abeta42 levels not only in AD but also in NAD. CONCLUSIONS: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.

Adult↗

PubMed1999

Apoptosis of T lymphocytes in acute disseminated encephalomyelitis.

Apoptosis has been shown to be an efficient mechanism involved in clearance of T lymphocytes from the brains of animals with acute experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. In this report we describe a case of acute disseminated encephalomyelitis following general measles infection. In this disease, which closely mimics the pathology of acute EAE we found a high percentage (30%) of apoptotic T cells. This indicates that in both rodent and human brain clearance of T cell-mediated inflammation follows similar mechanisms.

Adolescent↗

PubMed1999

Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death.

Neuronal loss is prominent in Alzheimer's disease (AD), and its mechanisms remain unresolved. Apoptotic cell death has been implicated on the basis of studies demonstrating DNA fragmentation and an up-regulation of proapoptotic proteins in the AD brain. However, DNA fragmentation in neurons is too frequent to account for the continuous neuronal loss in a degenerative disease extending over many years. Furthermore, the typical apoptotic morphology has not been convincingly documented in AD neurons with fragmented DNA. We report the detection of the activated form of caspase-3, the central effector enzyme of the apoptotic cascade, in AD and Down's syndrome (DS) brain using an affinity-purified antiserum. In AD and DS, single neurons with apoptotic morphology showed cytoplasmic immunoreactivity for activated caspase-3, whereas no neurons were labeled in age-matched controls. Apoptotic neurons were identified at an approximate frequency of 1 in 1100 to 5000 neurons in the cases examined. Furthermore, caspase-3 immunoreactivity was detected in granules of granulovacuolar degeneration. Our results provide direct evidence for apoptotic neuronal death in AD with a frequency compatible with the progression of neuronal degeneration in this chronic disease and identify autophagic vacuoles of granulovacuolar degeneration as possible means for the protective segregation of early apoptotic alterations in the neuronal cytoplasm.

Aged↗

PubMed1999

[Frontal lobe dementia. Clinical-pathologic case reports].

Frontal lobe dementia (FLD) is characterised clinically by personality changes and a progressive speech disorder finally leading to mutism. In the course of the disease also other neurological syndromes may occur such as parkinsonism, a partial Klüver-Bucy-syndrome or a degeneration of motoneurons (FLD + MND). The latter leads to death within about three years. The clinical diagnosis of FLD is supported by functional (SPECT) and morphological (CT, MRI) investigations. From 1988 to 1997, 9 cases of FLD (6 female, 3 male) were clinically diagnosed at our department of Gerontology, LNK Linz. In two of these cases the clinical diagnosis was confirmed histopathologically. Characteristically, all except one patients showed a presenile beginning of the disease. The clinical course was slowly progressive with a mean duration of about 10 years. Special attention was given to additional signs and symptoms of motor neuron disease, parkinsonism and hyperorality. Six patients suffered from FLD + MND; parkinsonism (rigid-akinetic type) and a partial Klüver-Bucy-syndrome were diagnosed in 5 cases each. In histopathological investigations the incidence of FLD seems to increase. This type of dementia should be considered as an important diagnosis differential of presenile dementia-syndromes.

Aged↗

PubMed1998

Biological markers for the diagnosis of Alzheimer's disease.

A diagnostic test for Alzheimer's disease (AD) based on biochemical markers in the cerebrospinal fluid can help improve diagnostic accuracy, which currently is approximately 90%, leaving every tenth AD patient undiagnosed or falsely diagnosed as having the disease. From all biochemical abnormalities described in AD patients, those related to the hallmark neuropathologic lesions, deposition of amyloid and formation of paired helical filaments mainly consisting of abnormally phosphorylated tau protein, are the most promising and the best documented, even though other markers bear some potential and remain to be further studied. Determining an increase of tau and a reduction of A beta 42 bears satisfactory, even though not absolute specificity for AD and represents a true aid for clinicians in diagnosing AD during the patients lifetime. It remains open if these markers will be helpful for the most challenging goal, diagnosing AD in the preclinical phase, when, according to morphological data, high amounts of these pathological proteins are already deposited in the brain tissue.

Aged↗

PubMed1998

Neuropathology of Alzheimer's disease: a critical update.

The unequivocal diagnosis of Alzheimer's disease (AD) rests on histopathological evidence at brain autopsy or biopsy. The morphology of AD includes cerebral atrophy, deposition of beta A4 amyloid (A beta) (senile plaques and amyloid angiopathy), neuritic changes (neuritic plaques, neurofibrillary tangles (NFT) and neuropil threads) with formation of paired helical filaments (PHF) containing polymerized hyperphosphorylated tau protein triplet, causing disruption of the neuronal cytoskeleton with loss of synapses and neurons, with altered cortico-cortical connectivity, leading to disconnection of the cerebral cortex. Defining criteria for the morphologic diagnosis of AD is difficult due to the phenotypic heterogeneity of the disease, the absence of specific markers, and overlap of AD morphology with that observed in non-demented elderly individuals. This gray zone between normal to pathologic aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the morphologic diagnosis of AD are based on (semi)quantitative assessment of diffuse and neuritic plaques (NIA), exclusively neuritic plaques (CERAD), plaques and NFT in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes (Braak and Braak, 1991); all of them have weaknesses and need to be revalidated. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging. Recent recommendations of the NIA-Reagan Institute for the morphologic diagnosis of AD are presented. Although the role of plaques and NFT in the pathogenesis of AD remains undetermined, clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best morphological signposts for AD. Recent studies on neuron death in AD that, at least in part, appears different from classical apoptosis and may precede the symptomatic stage of AD, have shown varying results indicating only indirect relationship between DNA fragmentation and both A beta deposition and NFTs. Both these AD-typical markers appear to increase the risk of cells to degenerate, but are not the sole responsibles of the degenerative process in AD, the basic mechanisms of which remain to be elucidated.

Aged↗

PubMed1998

Alzheimer disease: DNA fragmentation indicates increased neuronal vulnerability, but not apoptosis.

Although nerve cell loss is prominent in certain brain regions in Alzheimer disease (AD), it is currently unresolved how these cells die. Recent studies unanimously agree that there are more neurons displaying DNA fragmentation in AD compared with normal controls. However, controversy remains as to whether cell death is mediated by apoptosis or necrosis. We addressed this question by comparing AD lesions with those from cases with pontosubicular neuron necrosis (PSNN), a human pathological condition with unequivocal neuronal apoptosis, with regard to cell and nuclear morphology, immunohistochemistry, and in situ tailing. Immunohistochemistry was performed for an array of proteins with presumptive roles in the apoptotic process or the protection thereof, i.e. a recently described apoptosis-specific protein (ASP), the transcription factor c-Jun, Bcl-2, and various stress proteins: alpha B-Crystallin, heat shock protein (HSP) 27, HSP 65, HSP 70, HSP 90, and ubiquitin. Apoptotic neurons in PSNN displayed chromatin condensation, nuclear fragmentation, and cytoplasmic condensation. They were labeled with the in situ tailing technique and stained for the ASP. Despite the large numbers of cells with DNA fragmentation identified in the hippocampus of AD brains, only exceptional cells displayed the morphological characteristics of apoptosis or labeled for the ASP. We suggest that the increased rate of neuronal DNA fragmentation in AD patients indicates a higher susceptibility of the cells to metabolic disturbances compared with normal controls. The large number of cells with DNA fragmentation most likely reflects metabolic disturbances in the premortem period, and cell destruction is mediated through necrosis rather than apoptosis.

Aged↗

PubMed1998

Senile dementia with tangles (tangle predominant form of senile dementia).

Senile dementia with tangles is a sporadic subset of very late onset dementia with preponderance in females over age 80 years. Neuropathology shows diffuse cerebral atrophy with neurofibrillary tangles, often ghost tangles, and neuropil threads almost limited to limbic areas (transentorhinal, entorhinal area, hippocampuS--not exclusively sector CA 1--and amygdala) with only rare and mild involvement of the neocortex, basal ganglia and brainstem (except nucleus basalis and locus ceruleus), absence of neuritic plaques and absence or scarcety of amyloid deposits. This pattern of fibrillary pathology corresponds to Braak stages III and IV or the "limbic" type of Alzheimer disease that is considered the main form in the oldest-old but escapes the current criteria for the morphologic diagnosis of Alzheimer disease. It is distinct from other tau- or tangle-pathology related conditions, e.g. progressive supranuclear palsy, autosomal dominant dementia with tangles, and diffuse tangles with calcification. Very low prevalence of ApoE e4 allele (0.03-0.11%) and higher frequency of ApoE e3 and/or e2 suggest a lack of promoting effect of e4 and a possible protecting effect of e2/3 on amyloidogenesis. Senile dementia with tangles is suggested to be a variant of Alzheimer disease occurring in the oldest-old, but its nosological position within aging disorders of the brain is still controversy.

Alleles↗

PubMed1997

Mechanisms of cell death in Alzheimer's disease.

The etiology of Alzheimer's disease (AD) as well as its exact pathogenesis are unknown. Eventhough the deposition of beta A4 and the formation of neurofibrillary tangles represent impressive morphological hallmarks of the disease, several lines of evidence suggest that both lesions are not sufficient as causes of the neurodegenerative process. On the other hand, in vitro studies have shown that beta A4 is neurotoxic and is able to induce apoptotic cell death in neuronal cell cultures. Cells dying by apoptosis (programmed cell death) can be visualized in the tissue with a molecular biologic technique detecting fragmented nuclear DNA. Using this method, we have detected 50 x more neurons and 25 x more glial cells with nuclear DNA fragmentation in the brains of patients with AD than in non-demented controls. In contrast to previous studies, most of these cells did not reveal the characteristic morphological hallmarks of apoptosis. Most dying cells were not located within amyloid deposits and most dying cells did not bear a tangle. On the other hand, being in physical contact with an amyloid deposit increased the risk of a cell to dye by factor 5.7 and carrying a neurofibrillary tangle imposed a 3 times higher risk compared to unaffected nerve cells. Taken together, these data indicate that nerve cell death in AD occurs via a mechanism of programmed cell death different from classical apoptosis. Eventhough plaques and tangles increase the risk of cells to degenerate, both lesions are not the sole responsibles of the degenerative process, suggesting the existence of other factors that trigger the initiation of the cell death program in AD.

Aged↗

PubMed1997

Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia.

Apolipoprotein E (apoE) genotypes were analyzed in a subset of demented very old patients who share a uniform neuropathological picture consisting of various numbers of neurofibrillary tangles (NFT) in allocortical areas of the inferomedial temporal lobe without significant numbers of either diffuse amyloid or neuritic plaques. Among 18 patients with this condition referred to as NFT-predominant senile dementia (average age at death 87 +/- 4.7 years), we found allele frequencies of 0.11 epsilon 2, 0.86 epsilon 3 and 0.03 epsilon 4, which are significantly different from allele frequencies reported in Alzheimer's disease (0.04 epsilon 2, 0.59 epsilon 3 and 0.38 epsilon 4). The low prevalence of the apoE epsilon 4 allele in this subset of patients is striking and suggests that NFT-predominant senile dementia is a dementing neurodegenerative disease in which the deposition of A beta-amyloid did not occur, possibly due to protective effects of epsilon 2 and/or epsilon 3 alleles or lack of a promoting effect of apoE epsilon 4 on amyloidogenesis. We propose that NFT-predominant dementia is a variant of Alzheimer's disease occurring in the very old.

Aged↗

PubMed1997

Neuropathologic diagnosis of Alzheimer disease: consensus between practicing neuropathologists?

In an attempt to gather information on procedures, criteria, and possible difficulties, we have sent a detailed questionnaire on the postmortem diagnosis of Alzheimer disease (AD) to 169 neuropathologists in the German-speaking countries--Germany, Austria, and Switzerland. Of a total of 104 responses, 65 completed questionnaires were evaluated statistically. Fifty-nine percent of all respondents consider the neuropathologic diagnosis of AD a problem. Although 38% consider themselves able to establish the diagnosis without knowledge of clinical data, 29% do not believe this is possible. Thirty-eight percent opine that the presence of neurofibrillary tangles is not a prerequisite for a positive diagnosis, and 3% believe that examination of the hippocampal formation is unnecessary. For 6% of the respondents, neither a silver stain a silver stain nor thioflavin S is necessary. Ninety-seven percent believe that the availability of explicit diagnostic criteria would be helpful; by contrast, only 43% have exact knowledge of the National Institute of Aging criteria, and only 29% have exact knowledge of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Only every fourth neuropathologist uses these criteria regularly, and the validity of current diagnostic criteria is challenged by a considerable number of respondents. Many pathologists consider the quantification of plaques and tangles problematic, are confused by a lacking correlation of the pathology with the clinical picture, and believe that the gray zone between normal aging and full-fledged AD represents a major diagnostic problem. Our survey shows that there currently is no consensus on diagnostic procedures and criteria used in practice. This stresses the need for precise diagnostic guidelines and continuing information of actively practicing neuropathologists to achieve higher interlaboratory reliability of the diagnosis of AD.

Alzheimer Disease↗

PubMed1996

The apolipoprotein E epsilon 4 allele in Parkinson's disease with Alzheimer lesions.

The association between the apolipoprotein E (ApoE) epsilon 4 allele and Parkinson's disease (PD) with coexistent dementia has remained controversial. We determined ApoE allele frequencies in 35 subjects with neuropathologically confirmed Lewy body Parkinsonism with and without concomitant Alzheimer lesions, 27 patients with Alzheimer's disease (AD), and 54 controls without neurodegenerative disease. We hypothesized that if AD lesions in PD evolve by the same pathomechanism as in "pure AD," the ApoE epsilon 4 allele frequency in PD with AD lesions (PD+AD) and pure AD should be similar. The frequency of the ApoE epsilon 4 allele differed significantly between PD+AD (13.3%) and AD cases (35.2%), but not between PD+AD and PD without AD pathology (12.5%) or controls (11.1%). We conclude that the ApoE epsilon 4 allele does not function as a risk factor which influences the development of AD lesions in PD. Our data suggest that Parkinson's disease with Alzheimer lesions and Alzheimer's disease with coexistent Parkinsonian features represent two distinct entities at both the clinicopathological and molecular genetic levels.

Aged↗

PubMed1996

Tau protein and apolipoprotein E in CSF diagnostics of Alzheimer's disease: impact on non Alzheimer's dementia?

Tau protein and apolipoprotein E are suggested to be biochemically related to neurofibrillary tangles and senile plaques in Alzheimer's disease (AD) brains. They can be detected as immunoreactive material (total tau immunoreactivity [TTIR] and apolipoprotein E-immunoreactivity [ApoEIR]) in the cerebrospinal fluid (CSF). TTIR and ApoE-IR have been measured in ex vivo lumbar and post mortem ventricular CSF in AD, other neurological diseases without cognitive impairment, elderly depressive patients, and young and elderly controls. In lumbar CSF, there was a highly significant increase of TTIR and a minor, insignificant decrease of ApoE-IR in CSF of AD patients. The latter result was also found in ventricular CSF, whereas TTIR showed no significant difference between groups in the rostral CSF compartment. As depressive periods in the elderly may mimick a dementing process, these findings contribute to the differential diagnosis of these disorders by showing a different neurobiochemical CSF profile. Work in progress will include a variety of non-Alzheimer's dementias and possibly will further increase the value of CSF investigation in neurodegenerative disorders.

Adult↗

PubMed1996

Correlations between mental state and quantitative neuropathology in the Vienna Longitudinal Study on Dementia.

Quantitative clinicopathological correlation studies are one way to address the question of the relevance of morphological abnormalities in Alzheimer's dementia (AD). This paper summarizes results of the Vienna Longitudinal Study on Dementia obtained during the past few years and presents a critical discussion on the relevance of clinicopathological correlation studies for the pathogenesis of AD. Plotting of psychometric test scores against the numbers of plaques, tangles and neuropil threads in various cortical areas shows that significant correlations are due primarily to very high lesion counts in severely demented patients. These data indicate that neocortical neurofibrillary pathology can be considered an end-stage marker in the pathology of AD. On the other hand, the topographical staging of neuritic Alzheimer changes proposed by Braak and Braak (1991) appears to be a better reflection of the progression of the degenerative process than numerical lesion counts; there is a linear correlation between the Braak stages and Mini-Mental State scores in 122 aged individuals. Significant correlations are further obtained between the severity of dementia and the levels of a number of synaptic proteins including synaptophysin and the chromogranins. Taken together, our data suggest that none of the classical AD lesions, plaques and tangles, play a central role in the pathogenesis of dementia, a fact that is supported by a molecular biological study showing that there is no close relationship between these lesions and the neurons undergoing degeneration in AD. Whereas neuritic pathology is a useful histopathological marker for the diagnosis and staging of AD, the major correlate of cognitive deficits is the loss of corticocortical and subcorticocortical connections reflected by a depletion of synapses. This pathology may be induced by a mismetabolism of the beta-amyloid precursor proteins or their interaction with cytoskeletal proteins related to neuronal degeneration.

Aged↗

PubMed1996

Progressive supranuclear palsy: a clinicopathological study of 21 cases.

The symptoms and signs used to diagnose progressive supranuclear palsy (PSP) should be easily identifiable by neuropathologists and neurologists as well as by movement disorder experts. The presence, at the time of death, of symptoms and signs that are used in published clinical criteria for the diagnosis of this disorder was searched for in 21 pathologically confirmed typical PSP cases. The following items, present in at least 80% of pathologically confirmed cases, can be considered as the most accurate clinical data for the diagnosis of PSP: non-familial parkinsonism, not improved by L-dopa therapy, with vertical voluntary gaze palsy; postural instability and falls; pseudobulbar palsy and dementia with frontal lobe-like syndrome; and a progressive course of less than 10 years. The definite diagnosis of PSP must be clinicopathological, and these minimal clinical data may be used for this purpose.

Adult↗