[show abstract][hide abstract] ABSTRACT: Resorption of alveolar bone is the best recognized feature of mandibular aging in the edentate subject. The other consequences of the loss of teeth in the elderly are less well known. An anthropometric study of the mandible by antero-posterior and lateral radiographs of subjects older than 70 years both dentate and edentate but without any maxillo-mandibular dysmorphosis has been done to demonstrate the differences, which exist between the dentate and edentate mandible. The edentate mandibles showed a diminution in the height of the symphysis and increase in the height of the mandibular incisure. A diminution in the height of the body and an increase in the gonial angle in the significant manner. No significant difference was seen for the height of the ramus and the length of the mandible, the minimum width of the ramus and the bigonial width. The diminution in the height of the mandibular symphysis and of the body is explained by the resorption of the alveoli part of the mandible. The increase in the mandibular angle and the diminution in the height of the mandibular incisure may be explained by disequilibrium between the elevator and depressor muscles of the mandible, as a function of the elevator muscles or by the absence of the molar buttress.
Surgical and Radiologic Anatomy 12/2005; 27(4):265-70. · 1.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been proposed that, independent of the epsilon4 allele, APOE promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for Alzheimer's disease by modulating APOE expression.
To measure the level of APOE expression in Alzheimer's disease.
Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer's disease in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes.
An inverse correlation between APOE expression level and A beta loads was observed. As previously described and extended to 114 cases here, an association between the -219 TT genotype and a higher level of parenchymal A beta deposition was found, irrespective of APOE epsilon4 allele status. This effect was more pronounced in older individuals, whereas higher A beta load appeared more closely related to epsilon4 in the younger age group (cut off point at the median age at death (72.5 years)). The -219 TT genotype was associated with a decrease in APOE expression. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p = 0.01).
In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T polymorphism, may influence risk and constitute a determinant A beta load in Alzheimer's disease.
[show abstract][hide abstract] ABSTRACT: Although possession of the epsilon 4 allele of the apolipoprotein E gene appears to be an important biological marker for Alzheimer's disease (AD) susceptibility, strong evidence indicates that at least one additional risk gene exists on chromosome 12. Here, we describe an association of the 3'-UTR +1073 C/T polymorphism of the OLR1 (oxidised LDL receptor 1) on chromosome 12 with AD in French sporadic (589 cases and 663 controls) and American familial (230 affected sibs and 143 unaffected sibs) populations. The age and sex adjusted odds ratio between the CC+CT genotypes versus the TT genotypes was 1.56 (p=0.001) in the French sample and 1.92 (p=0.02) in the American sample. Furthermore, we have discovered a new T/A polymorphism two bases upstream of the +1073 C/T polymorphism. This +1071 T/A polymorphism was not associated with the disease, although it may weakly modulate the impact of the +1073 C/T polymorphism. Using 3'-UTR sequence probes, we have observed specific DNA protein binding with nuclear proteins from lymphocyte, astrocytoma, and neuroblastoma cell lines, but not from the microglia cell line. This binding was modified by both the +1071 T/A and +1073 C/T polymorphisms. In addition, a trend was observed between the presence or absence of the +1073 C allele and the level of astrocytic activation in the brain of AD cases. However, Abeta(40), Abeta(42), Abeta total, and Tau loads or the level of microglial cell activation were not modulated by the 3'-UTR OLR1 polymorphisms. Finally, we assessed the impact of these polymorphisms on the level of OLR1 expression in lymphocytes from AD cases compared with controls. The OLR1 expression was significantly lower in AD cases bearing the CC and CT genotypes compared with controls with the same genotypes. In conclusion, our data suggest that genetic variation in the OLR1 gene may modify the risk of AD.
Journal of Medical Genetics 07/2003; 40(6):424-30. · 5.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recently, a polymorphism located in the promoter of the presenilin 1 gene was associated with early-onset Alzheimer disease (EOAD). To determine if this polymorphism is also a risk factor for late-onset Alzheimer's disease (LOAD), we analysed its potential impact in a French population of LOAD patients only. Genotype and allelic distributions of the -48CT polymorphism were similar for controls and AD patients. Our result suggests that this polymorphism may not influence the development of LOAD. Other studies need to be undertaken to confirm this association restricting the impact of this polymorphism to EOAD patients.
Journal of Neural Transmission 08/2002; 109(7-8):1023-7. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is evidence that inflammatory processes may contribute to the development of Alzheimer's disease through production of cytokines and free radicals that damage neurones. A recent study has shown that transforming growth factor beta1 (TGF-beta1) signalling in astrocytes promotes Abeta production and could play a critical role in the formation of amyloid plaques in the brain.
To explore the impact of the -800 and -509 TGF-beta1 promoter polymorphisms and the +25 polymorphism on the risk of occurrence of Alzheimer's disease in a large population of sporadic cases and controls, and on the amyloid beta (Abeta) load in the brains of Alzheimer patients.
The TGF-beta1 genotypes of the three polymorphisms were determined in 678 sporadic Alzheimer's disease patients and 667 controls. They were also characterised, along with Abeta load, in the brains of 81 necropsy confirmed Alzheimer patients.
No significant variations in the distribution of the genotypes and haplotypes were observed between Alzheimer patients and controls, or in the amount of Abeta deposition.
These results do not suggest an influence of genetic variability at the TGF-beta1 gene locus on the occurrence of Alzheimer's disease.
[show abstract][hide abstract] ABSTRACT: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele.
Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied.
Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification.
The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population.
The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.
[show abstract][hide abstract] ABSTRACT: The FE65 protein was previously described interacting with amyloid protein precursor (APP) and mediating its internalization. Hu et al. (Hum. Genet., 103 (1998) 295) recently reported that a deletion polymorphism in intron 13 of the FE65 gene may be protective for sporadic Alzheimer's disease (AD) forms and suggested that this deletion may modify splicing between exon 13 and 14 (the two exons encoding the interaction domain of FE65 with APP). We tested the impact of this polymorphism in 646 controls and 639 sporadic AD cases. We were only able to detect a protective effect of the deletion in the population over 75 years (odds ratio = 0.53, 95% confidence interval (0.35-0.82), P= 0.002). Furthermore, no association of this polymorphism with Abeta40, Abeta42(43) and total Abeta loads were detected in 74 AD brains, although, we could expect that this deletion was associated with modifications of the APP metabolism. In conclusion, the FE65 gene may be a minor genetic determinant only for sporadic late-onset AD forms, although, we cannot conclude that this impact is mediated by a modulation of the APP process and/or Abeta peptide deposition.
[show abstract][hide abstract] ABSTRACT: Recent reports have suggested that variability in the alpha2-macroglobulin gene is a genetic risk factor for Alzheimer's disease. Here we have both tested a common polymorphism in the gene (I1000V) for association with the disease in a four-site case control study design, and tested the locus for linkage in a large series of sibpairs afflicted with late onset disease. Our results fail to show an association between this polymorphism and disease.
[show abstract][hide abstract] ABSTRACT: Possession of the apolipoprotein E (APOE) epsilon4 allele is the most frequently associated genetic susceptibility factor for Alzheimer's disease (AD). Recently, new polymorphisms in the regulatory region of the APOE gene have been described. We analysed the effects of three of these mutations (-491 AT, -427 CT and Th1/E47cs) on disease risk in a large case-control study, and tested their impacts on APOE allelic expression in brain tissues. The Th1/E47cs T allele was associated with an increased risk of occurrence of AD, while the -491 T allele was associated with a decreased risk, independently of the APOE epsilon2/epsilon3/epsilon4 polymorphism effect. However, the impact of the Th1/E47cs mutation was the strongest. The -427 CT polymorphism was not associated with the disease. In AD subjects heterozygous for the epsilon4 allele, analysis of allelic expression showed that the relative expression levels of the epsilon4 allele were higher than those of the corresponding controls. Consistent with epidemiological data, the relative level of expression of the epsilon4 allele was modified accordingly to the presence or absence of the two main promoter polymorphisms, indicating, in vivo, the deleterious effect of the Th1/E47cs T allele and the protective effect of the -491 T allele in population. These data indicate that in addition to the qualitative effect of the APOE epsilon2/epsilon3/epsilon4 polymorphisms on the AD occurrence, the quantitative variation of expression of these alleles due to functional APOE promoter mutations, is a key determinant of AD development.
Human Molecular Genetics 10/1998; · 7.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: The epsilon4 allele of the Apolipoprotein E gene (APOE), one of the main allele of APOE polymorphism, is a major risk factor for the development of Alzheimer's disease. However, several data suggest that genetic factors, within the APOE locus, may also modulate the risk associated with this polymorphism. We look for new mutations in the APOE promoter, susceptible to modify the risk associated with the APOE epsilon4 allele. We characterised a G-->T mutation at -186 bp of the APOE gene TATA box, named Th1/E47cs. This new polymorphism is located in a consensus sequence of a potential transcriptional (Th1/E47) factor binding site. We studied the impact of this new polymorphism with those of other markers of the APOE locus in a large case-control study and observed that Th1/E47cs modulated the influence of the APOE epsilon4 allele on the risk of Alzheimer's disease.
Human Molecular Genetics 03/1998; 7(3):533-40. · 7.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: 1. The presence of Alzheimer-type neurofibrillary pathology and amyloid deposits within the brains of 27 aged non-demented subjects was investigated by immunoblotting and immunohistochemistry using antibodies directed against pathological Tau proteins 55, 64 and 69 and beta A4 respectively. 2. The abnormal Tau triplet, a biochemical marker of neurofibrillary degeneration was quantified by western blot and densitometric analysis in several cortical areas including the entorhinal cortex (EC), hippocampus and Brodmann areas (BA) 38, 20, 22, 35, 9, 44 and 39. 3. The abnormal Tau triplet was detected in the EC and the hippocampus of most of the controls aged over 70 years. In few control cases abnormal Tau proteins were also detected in the isocortex, in BA38 alone or also in BA20. Some cases and especially those with Tau pathology in the temporal lobe contained numerous senile plaques (SP) in the neocortex. 4. The authors conclude that control cases with Tau pathology in the temporal lobe and numerous SP in the neocortex were likely to be subclinical stages of AD whereas others with Tau pathology exclusively detected in the EC and hippocampus and without or few SP in the neocortex were related to normal aging.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/1995; 19(6):1035-47. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glial fibrillary acidic protein (GFAP), a biochemical marker of astrocytes and glial reaction, was quantified in different brain areas from 16 non-demented patients with a mini mental state score > 25/30 and aged from 21 to 95 years. For each brain, we analyzed the hippocampus (H), the parahippocampus gyrus (GPH) and the neocortical Brodmann areas 9, 22, 39, 44. The quantification of GFAP was performed on the different brain homogenates treated with SDS, using a Western blot method and an immunodetection with a monoclonal antibody against human GFAP. The quantity of GFAP found in the hippocampus and the parahippocampal region were significantly increased as a function of age (p < 0.001). This was not observed for neocortical areas. It has been shown that hippocampal and parahippocampal regions are specifically affected by the Alzheimer-type degenerating process during aging. Glial reaction, as visualized by immunoblotting, could be directly linked to this phenomenon.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 08/1994; 317(8):749-53.
[show abstract][hide abstract] ABSTRACT: An immunoblot study was performed in several cortical samples from non-demented aged controls and compared with those from Alzheimer patients, using antibodies against Tau 55, 64 and 69, which are specific and reliable markers of the neurofibrillary degeneration of the Alzheimer type. The immunodetection of Tau 55, 64 and 69 was positive in all cortical areas from Alzheimer patients, in the entorhinal cortex from each control aged more than 65 but not in cortical samples from younger controls. We demonstrate that the entorhinal cortex is the most vulnerable neuronal population in aging and that the biochemical dysfunctions observed in this area are typically of the 'Alzheimer-type'.
[show abstract][hide abstract] ABSTRACT: A biochemical mapping of neurofibrillary degeneration was performed in Brodmann areas of the brains of five patients with senile dementia of the Alzheimer type (AD). To quantify the degenerating process, we used an immunoblot method with antibodies directed against the abnormally phosphorylated tau proteins named Tau 55, 64 and 69, known to be early and reliable markers of the degenerating process in AD. The detection intensities were assessed using a numerical rating scale for each area and scores were grouped by lobe. In all cases, the detection of Tau 55, 64 and 69 was positive in all areas except in primary visual cortex (area 17) for two patients. The detections were especially strong in temporal neocortical and limbic areas and were higher in associative cortex than in primary sensory cortex. Scores from the occipital and frontal lobes differed strongly between patients as compared to the uniform degree of detection in the limbic, temporal and parietal lobes. Despite a relatively identical duration of the disease and an apparently global involvement of the cerebral cortex, the distribution of neurofibrillary degeneration in AD varies significantly across cortical areas and displays striking heterogeneity patterns along the rostrocaudal axis. The immunodetection of abnormal tau proteins using the Western blot method may provide complete and rapid quantitative data of the degenerating process in AD.