Biomedical subjects

C Bouras

Publications and source records attributed to C Bouras.

At least 37 records · Page 2Linked to original sources

PubMed2000

Neural substrates of spatial and temporal disorientation in Alzheimer's disease.

To examine the neuroanatomical correlates of spatial and temporal disorientation in Alzheimer's disease (AD), we performed an anterograde clinicopathological study of 29 patients with clinically and neuropathologically confirmed AD. Spatial and temporal disorientation was assessed using the locational orientation subtests of the Mini Mental State Examination and the Benton's test for temporal orientation. Quantitative analysis of neurofibrillary tangles and senile plaques were performed in the CA1 field of the hippocampus, layers II and V of the entorhinal cortex, and layers II-III and V-VI of areas 9, 7, 39, 19, 37, 20 and 23 in the right hemisphere. Forward stepwise logistic regression was used to assess the relationship between lesion densities and the presence of either spatial or temporal disorientation; severity scores and brain weight were included as covariants. A statistically significant relationship was found between neurofibrillary tangle densities in Brodmann's areas 7, 23 and the CA1 field of hippocampus and both spatial and temporal disorientation. Senile plaque counts did not correlate with any of the neuropsychological parameters. Both temporal and spatial disorientation in AD are related to the degeneration of the same pathways linking the hippocampus with the superior parietal and posterior cingulate cortex in the right hemisphere. These observations are discussed with respect to the notion of global corticocortical disconnection in AD.

Aged↗

PubMed2000

Differential messenger RNA distribution of lactate dehydrogenase LDH-1 and LDH-5 isoforms in the rat brain.

The role of lactate in brain energy metabolism has recently received renewed attention. Although blood-borne monocarboxylates such as lactate poorly cross the blood-brain barrier in the adult brain, lactate produced within the brain parenchyma may be a suitable substrate for brain cells. Lactate dehydrogenase is crucial for both the production and utilization of lactate. In this article, we report the regional distribution of the messenger RNAs for lactate dehydrogenase isoforms 1 and 5 in the adult rat brain using in situ hybridization histochemistry with specific [alpha-(35)S]dATP 3' end-labeled oligoprobes. The autoradiographs revealed that the lactate dehydrogenase-1 messenger RNA is highly expressed in a variety of brain structures, including the main olfactory bulb, the piriform cortex, several thalamic and hypothalamic nuclei, the pontine nuclei, the ventral cochlear nucleus, the trigeminal nerve and the solitary tractus nucleus. In addition, the granular and Purkinje cell layers of the cerebellum showed a strong labeling. The neocortex (e.g., cingular, retrosplenial and frontoparietal cortices) often exhibits a marked laminar pattern of distribution of lactate dehydrogenase-1 messenger RNA (layers II/III, IV and VI being most strongly labeled). In contrast, expression of the lactate dehydrogenase-5 messenger RNA generally seemed more diffusely distributed across the different brain regions. Expression was particularly strong in the hippocampal formation (especially in Ammon's horn and dentate gyrus) and in the cerebral cortex, where no laminar pattern of distribution was observed. Overall, these data are consistent with the emerging idea that lactate is an important energy substrate produced and consumed by brain cells.

Animals↗

PubMed2000

Immediate causes of death of demented and non-demented elderly.

OBJECTIVE: To investigate the immediate causes of death, in autopsied demented and non-demented elderly. DESIGN: Retrospective clinicopathologic correlations. SETTING: Acute and intermediate care geriatric hospital. PARTICIPANTS: 342 hospitalized demented and non-demented elderly (mean age 84.94 +/- 6.9 years) who underwent consecutive postmortem examinations: 120 demented patients with either vascular dementia (VaD, n = 34), mixed dementia (MD, n = 65) or Alzheimer's disease (AD, n=21) neuropathologically confirmed and 222 nondemented elderly. RESULTS: Primary causes of death were similar in both demented and non-demented patients; the commonest were cardiovascular disease and bronchopneumonia. Cardiac causes of death and especially cardiac failure were more frequent in VaD than in AD or MD (respectively P = 0.027 and 0.005). Dementia was an underlying but never a primary cause of death. CONCLUSIONS: Immediate causes of death are similar in elderly demented and non-demented patients.

Aged↗

PubMed2000

A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.

We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.

Adult↗

PubMed2000

Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors.

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

Adult↗

PubMed1999

Neuroanatomic correlates of visual agnosia in Alzheimer's disease: a clinicopathologic study.

OBJECTIVE: To examine the neuroanatomic correlates of visual agnosia in AD. METHODS: The authors performed an anterograde clinicopathologic study of 23 patients with clinically and neuropathologically confirmed AD in a 305-bed acute care geriatric hospital and a 165-bed acute care psychiatric hospital. The presence of apperceptive visual agnosia was assessed using the Ghent's overlapping figure test and the Gottschaldt's hidden figure test. Associative visual agnosia was examined using the conceptual items of the Columbia Mental Maturity Test. Correlations between neurofibrillary tangle (NFT) and senile plaque (SP) densities and visual agnosia were studied using forward stepwise logistic regression. RESULTS: A statistically significant relation was found between NFT densities in Brodmann's areas 18, 19, and 37, and associative visual agnosia, whereas NFT densities in the areas studied did not correlate with the presence of apperceptive visual agnosia. Senile plaque counts did not correlate with any of the neuropsychological parameters. CONCLUSIONS: These results support the existence of a dichotomy between associative and apperceptive agnosia, and show that only the former is related to the damage of secondary and high-order visual association areas in AD. In addition, the results suggest that SP densities do not represent a valuable pathologic correlate of visual agnosia in this disorder.

Aged↗

PubMed1999

Differential distribution of presenilin-1, Bax, and Bcl-X(L) in Alzheimer's disease and frontotemporal dementia.

We have previously reported that presenilin-1 (PS-1)-immunoreactive neurons survive in late-onset sporadic Alzheimer's disease (AD). To examine if this is also the case in other dementing conditions, and if it is associated with changes in the expression of the main apoptosis-related proteins, a quantitative immunocytochemical study of presenilin-1, Bax, and Bcl-X(L) in the cerebral cortex of non-demented and AD patients, and patients with frontotemporal dementia (FTD) was performed. In non-demented cases, the frequency of neurons showing PS-1 immunoreactivity was 25-60%, Bax immunoreactivity 36-54%, and Bcl-X(L) immunoreactivity 26-63% depending on the cortical area. The frequency of NFT-free neurons which contained PS-1 or Bax was consistently increased in all of the areas in AD. In FTD cases, the percentage of PS-I-, but not Bax-immunoreactive neurons was increased only in areas displaying a substantial neuronal loss. Conversely, there was no difference in the densities of Bcl-X(L)-containing neurons among the three diagnosis groups. These data suggest that surviving neurons in affected cortical areas in AD show a high expression of PS-1 and Bax, indicating that these proteins play a key role in the mechanisms of cell death in this disorder. In FTD, neurons containing PS-1 are preserved, further supporting a neuroprotective role for this protein in other neurodegenerative disorders.

Aged↗

PubMed1999

Presenilin-1 expression in Pick's disease.

Recent studies have reported that neuronal populations expressing low levels of presenilin-1 (PS-1) display increased vulnerability in late-onset sporadic Alzheimer's disease (AD). To examine whether this phenomenon also occurs in other neurodegenerative diseases, we performed a quantitative immunocytochemical study of PS-1 distribution in the cerebral cortex of Pick's disease (PiD) cases and non-demented individuals. In PiD cases, the percentage of PS-1-containing, Pick body (PB)-free neurons was significantly elevated only in cortical areas showing neuronal loss. In these areas, PS-1 levels, measured by immunoblotting, were often higher in PiD compared to non-demented cases. Moreover, PS-1 immunoreactivity was significantly reduced in PB-containing neurons. These data suggest that as previously shown in AD, low cellular expression of PS-1 may be associated with increased neuronal loss and cellular degeneration.

Aged↗

PubMed1999

Mapping of cocaine and amphetamine regulated transcript (CART) mRNA expression in the hypothalamus of elderly human.

The expression of cocaine and amphetamine regulated transcript (CART) in the hypothalamus of aged humans was studied by in situ hybridization histochemistry. Formalin fixed coronal sections through the hypothalamus were hybridized with [35S]dATP 3' end-labeled deoxyoligonucleotide probes complementary to sequences of the CART encoding gene. Large populations of cells expressing CART messenger RNA were mainly detected in the paraventricular nucleus of the hypothalamus. Other hypothalamic subdivisions displaying numerous radiolabeled cells were the dorsomedial, ventromedial, infundibular and tuberomammillary nuclei, and the dorsal hypothalamic area. Additionally, a few labeled cells were observed in the perifornical and lateral hypothalamic areas. Hybridizing cells were occasionally seen in the supraoptic nucleus. Overall, the pattern of distribution of CART expressing cells observed throughout the human hypothalamus, with few exception, e.g. the supraoptic nucleus, is comparable to that previously reported in the rat brain. These anatomical results suggest that in human, hypothalamic CART expression could be involved a variety of neuroendocrine functions including food-intake.

Aged↗

PubMed1998

Selective vulnerability of neocortical association areas in Alzheimer's disease.

This article reviews the possible relationships between the localization of cellular pathologic changes in Alzheimer's disease (AD), and the distribution of neuronal components of the neocortical circuitry that are affected by these alterations. In particular, evidence from the study of large autopsy series supporting the role of the inferior temporal cortex as a key area in the progression of the dementing process is presented. The notion of selective vulnerability in AD at the level of affected neocortical association areas, layers, and specific cell populations is discussed to provide insight into the molecular background of the development of neurofibrillary tangles within the cerebral cortex. Moreover, recent data on pathological correlates of apraxia in AD are examined in the light of the hypothesis of global corticocortical disconnection in this disorder.

Age Factors↗

PubMed1998

Imidazoline receptor proteins in brains of patients with Alzheimer's disease.

Imidazoline receptors (29/30- and 45-kDa proteins) were quantitated in postmortem brains of patients with Alzheimer's disease (AD) by using immunoblotting techniques and a specific antiserum. Increased levels of the 29/30-kDa protein (30%), 45-kDa protein (36%) and glial fibrillary acidic protein (88%) were found in the frontal cortex of AD patients. These findings are in line with the reported higher density of imidazoline receptors labelled by [3H]idazoxan in AD brains, suggesting that these imidazoline receptor proteins are related to the I2-imidazoline receptor located in mitochondria of glial (astrocyte) cells.

Aged↗

PubMed1998

Pathologic correlates of apraxia in Alzheimer disease.

OBJECTIVE: To examine the neuroanatomical correlates of apraxia in Alzheimer disease. PATIENTS: Twenty-three patients with clinically overt Alzheimer disease. DESIGN: Anterograde study and neuropathologic case series. Clinical severity was assessed using the Global Deterioration Scale. Ideomotor praxis was examined on transitive and intransitive movements and meaningless gestures, and dressing ability was evaluated clinically. Constructive praxis was tested using a 3-dimensional figure copying task. Correlations between neurofibrillary tangle and senile plaque densities and praxis test performance were studied using stepwise logistic regression models. SETTING: Studies were conducted at the Psychiatric and Geriatric Hospitals of the University of Geneva School of Medicine, Geneva, Switzerland. MAIN OUTCOME MEASURES: Odds ratios to estimate the associations between neurofibrillary tangle and senile plaque densities in each neocortical area and the presence of ideomotor, dressing, and constructional apraxia. RESULTS: Statistically significant relationships were found between neurofibrillary tangle densities in the anterior cingulate cortex and ideomotor and dressing apraxia and between neurofibrillary tangle densities in the superior parietal, posterior cingulate, and occipital cortex and constructional apraxia. Senile plaque counts did not correlate with praxic performance. CONCLUSIONS: These results suggest that ideomotor and dressing apraxia are associated with mild damage of the anterior cingulate cortex, whereas constructional apraxia is related to the disruption of cortical pathways mediating visuospatial cognition in Alzheimer disease. Senile plaque densities do not represent a valuable pathologic correlate of apraxia in this disorder.

Aged↗

PubMed1998

Possible neuroprotective role of clusterin in Alzheimer's disease: a quantitative immunocytochemical study.

Clusterin is a secreted glycoprotein that is expressed in response to tissue injury both in peripheral organs and in the brain. Recent studies have shown a substantial increase in clusterin mRNA in pyramidal neurons of the hippocampus and the entorhinal cortex in Alzheimer's disease (AD), with clusterin immunoreactivity occurring in neuropil threads, neurofibrillary tangles (NFT), and senile plaques. To elucidate further the role of this protein in the degenerative process, a quantitative study of its distribution in the cerebral cortex of non-demented and AD patients, all older than 85 years of age, was performed using immunocytochemistry. Using a stereological approach, we found that in cortical areas affected in AD, such as the entorhinal, inferior temporal and superior frontal cortices, the percentage of NFT-free neurons displaying clusterin immunoreactivity was significantly higher than that in non-demented cases. No such increase in the density of clusterin-immunoreactive neurons was seen in cortical areas that were less affected in the disease process. Furthermore, clusterin immunoreactivity was rarely observed in NFT-containing neurons. In conjunction with previous observations in peripheral tissues, these data suggest that clusterin may have a neuroprotective role, and that in AD, low cellular expression of this protein may be associated with neuronal degeneration and death.

Aged↗

PubMed1998

Comparative distribution of nitric oxide synthase- and serotonin-containing neurons in the raphe nuclei of four mammalian species.

Monoclonal antibodies were generated against serotonin (5-HT) and the C-terminal portion of the neuronal form of nitric oxide synthase (nNOS), the enzyme producing nitric oxide in neurons. These antibodies were used to compare the distribution of 5-HT- and nNOS-containing neurons in the raphe nuclei of four animal species (rat, mouse, guinea pig, and cat). It was found that the rat was the only species in which the raphe nuclei contain a substantial number of nNOS-immunoreactive (IR) cell bodies. In this species and as observed by other authors, all mesencephalic raphe nuclei contained nNOS-IR cells, the largest group being located in the nucleus raphe dorsalis. The coexistence of nNOS and 5-HT immunoreactivities in these nuclei was visualized by double labeling. In the medulla, the nuclei raphe magnus and obscurus displayed a rather low number of nNOS-IR neurons. In the other species, nNOS-IR cell bodies were found in very low numbers, whatever raphe nucleus was considered. The rostral pole of the nucleus raphe dorsalis and the nuclei raphe magnus and obscurus contained a few nNOS-IR neurons which did not show any coincidence with the 5-HT neurons. In addition, nNOS-IR axons were rare. It is concluded that in the mouse, guinea pig, and cat the involvement of nitric oxide in functions subserved by 5-HT within the raphe nuclei might be minimal.

Animals↗

PubMed1998

Arguments against the involvement of Borrelia burgdorferi sensu lato in Alzheimer's disease.

The involvement of spirochaetes, such as the aetiologic agent of Lyme borreliosis, Borrelia burgdorferi sensu lato, in Alzheimer's disease (AD), a common neuropathology, has been proposed by several groups in the past. In our laboratory, brains from 10 AD patients were analysed for the presence of B. burgdorferi sensu lato by both standard and nested PCR techniques based on various target regions, such as the hbb gene (encoding the histone-like protein HBb), the fla gene (flagellin), the rrl-rrf ribosomal intergenic spacer region and the rrs gene (encoding 16S rRNA). In addition, ELISA and Western blot tests for the detection of antibodies against spirochaetal antigens were performed on 27 sera from clinical AD patients. Using these methods, we did not obtain any evidence of the involvement of B. burgdorferi in Alzheimer's disease.

Aged↗

PubMed1998

Re-evaluating the role of vascular changes in the differential diagnosis of Alzheimer's disease and vascular dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia, and much effort has been devoted to their differential diagnosis. However, current epidemiological, clinical and neuropathological evidence points to a substantial overlap between AD and VaD and suggests that vascular pathology, the traditional cornerstone of the differential diagnosis between the two entities, may not represent as clear a line of demarcation as originally believed. It may be time to reevaluate the dichotomy between AD and VaD.

Alzheimer Disease↗

PubMed1998

Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle.

Mounting evidence from in vitro experiments indicates that lactate is an efficient energy substrate for neurons and that it may significantly contribute to maintain synaptic transmission, particularly during periods of intense activity. Since lactate does not cross the blood-brain barrier easily, blood-borne lactate cannot be a significant source. In vitro studies by several laboratories indicate that astrocytes release large amounts of lactate. In 1994, we proposed a mechanism whereby lactate could be produced by astrocytes in an activity-dependent, glutamate-mediated manner. Over the last 2 years we have obtained further evidence supporting the notion that a transfer of lactate from astrocytes to neurons might indeed take place. In this article, we first review data showing the presence of mRNA encoding for two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Second, by using monoclonal antibodies selectively directed against the two distinct lactate dehydrogenase isoforms, LDH1 and LDH5, a specific cellular distribution between neurons and astrocytes is revealed which suggests that a population of astrocytes is a lactate 'source' while neurons may be a lactate 'sink'. Third, we provide biochemical evidence that lactate is interchangeable with glucose to support oxidative metabolism in cortical neurons. This set of data is consistent with the existence of an activity-dependent astrocyte-neuron lactate shuttle for the supply of energy substrates to neurons.

Animals↗

PubMed1998

Cellular vulnerability in brain aging and Alzheimer's disease. Clinical correlates and molecular background.

The neuropathological changes associated with normal brain aging and Alzheimer's disease involve specific cortical circuits. Extensive hippocampal alterations are correlated with age-associated memory impairment, while substantial neurofibrillary tangle formation in neocortical association areas of the temporal lobe is a prerequisite for the development of Alzheimer's disease. Several lines of evidence indicate that there is no correlation between senile plaque densities and the degree of dementia in this disorder. The cortical involvement in the ninth and tenth decades of life is different from that observed in younger patients in that parietal and cingulate areas are affected early in the course of Alzheimer's disease, and neocortical senile plaques densities are strongly correlated with the severity of dementia. Moreover, Alzheimer's disease pathology is characterized in these very old patients by high neurofibrillary tangle densities in the anterior CA1 field, but not in the entorhinal cortex and inferior temporal cortex. These patterns of lesion distribution are discussed in respect to the neurochemical, genetic and metabolic factors which may influence the neuronal vulnerability in Alzheimer's disease.

Aged↗