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John Hardy - One of the best experts on this subject based on the ideXlab platform.
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estimation of the genetic contribution of presenilin 1 and 2 mutations in a population based study of presenile alzheimer disease
Human Molecular Genetics, 1998Co-Authors: Marc Cruts, Marleen Van Den Broeck, John Hardy, H Backhovens, Cornelia M Van Duijn, A Wehnert, Sally Serneels, R Sherrington, Mike Hutton, Peter St GeorgehyslopAbstract:Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with Onset Age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkAge analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in Onset Ages above 55 years, with one segregating in an autosomal dominant family with mean Onset Age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with Onset Age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.
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apoe genotype does not modulate Age of Onset in families with chromosome 14 encoded alzheimer s disease
Neuroscience Letters, 1994Co-Authors: Christine Van Broeckhoven, H Backhovens, Marc Cruts, Jean Jacques Martin, Richard Crook, H Houlden, John HardyAbstract:Abstract A recent study has demonstrated an association of the apolipoprotein E allele ɛ4 (APOE*4) to familial and sporadic late-Onset Alzheimer's disease (AD). Also, in late-Onset AD families linked to chromosome 19, the Onset Age decreased when the number of APOE*4 alleles increased. A similar effect of the APOE*4 genotype was observed in early-Onset AD families linked to mutations in the APP gene located on chromosome 21. We assessed whether the APOE genotype had an influence on the Age of Onset of AD in chromosome 14 linked early-Onset AD families. No significant effect of the APOE genotype on Onset Age could be detected.
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Genetics of Alzheimer's disease: APP, APOE, and the chromosome 14 locus
Neuropsychopharmacology, 1994Co-Authors: John HardyAbstract:At least three genetic loci can predispose towards AD. These are the APP gene, the ApoE gene and a locus on chromosome 14. Besides summarizing the role of APP mutations in disease pathogenesis, I shall present 4 series of analyses. 1) data indicating that ApoE genotype modulates Onset Age around 55 years in families with APP mutations with ApoE4 causing an earlier, and ApoE2 a later Onset Age relative to ApoE3. 2) data indicating that ApoE genotype does not modulate Onset Age in families with chromosome 14 locus encoded AD. 3) data confirming that ApoE4 shows a strong association with late Onset AD. 4) genetic information confirming, but not further refining the position of the locus causing very early Onset AD located between D14S52 and D14S55. These data have been generated in collaborations with the Dementia and Prion groups at St. Mary's Hospital, London, the Alzheimer's Group at the Karolinska Institute, Sweden, the Department of Pathology, at the University of Helsinki, Finland and the Alzheimer's Genetic Group at the University of Antwerp, Belgium.
Thomas V. Lowell - One of the best experts on this subject based on the ideXlab platform.
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questioning the Age of the moorhead phase in the glacial lake agassiz basin
Quaternary Science Reviews, 2006Co-Authors: Timothy G. Fisher, Thomas V. LowellAbstract:Abstract The stratigraphy of sites within the Lake Agassiz basin that constrain the timing of the Onset of the Moorhead low-water Phase is reexamined. Stratigraphic interpretation of the oldest date (10,960 14 C yr BP) from cross-bedded sand of the Ojata Beach is questioned, particularly in light of demonstrated long-distance transport and reworking of older organic material from elsewhere in the basin. A maximum Onset Age for the Moorhead Phase is suggested from a 10,675±60 14 C yr BP Age from wood in gravel from the base of the southern outlet, whereas radiocarbon dates from in situ peat indicate a later minimum Onset Age of 10,340±100 14 C BP.
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rapid communication questioning the Age of the moorhead phase in the glacial lake agassiz basin
2006Co-Authors: Timothy G. Fisher, Thomas V. LowellAbstract:The stratigraphy of sites within the Lake Agassiz basin that constrain the timing of the Onset of the Moorhead low-water Phase is reexamined. Stratigraphic interpretation of the oldest date (10,960 14 C yr BP) from cross-bedded sand of the Ojata Beach is questioned, particularly in light of demonstrated long-distance transport and reworking of older organic material from elsewhere in the basin. A maximum Onset Age for the Moorhead Phase is suggested from a 10,675760 14 C yr BP Age from wood in gravel from the base of the southern outlet, whereas radiocarbon dates from in situ peat indicate a later minimum Onset Age of 10,3407100 14 C BP.
Yunting Chang - One of the best experts on this subject based on the ideXlab platform.
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comorbidity profiles among patients with alopecia areata the importance of Onset Age a nationwide population based study
Journal of The American Academy of Dermatology, 2011Co-Authors: Yiju Chen, Weicheng Tseng, Tzengji Chen, Chianyaw Hwang, Chihchiang Chen, Yunting ChangAbstract:Background Alopecia areata (AA) is considered an autoimmune disease with undetermined pathogenesis. Age at Onset predicts distinct outcomes. A nationwide study of the relationship of AA with associated diseases stratified by Onset Age has rarely been reported. Objective We sought to clarify the role of atopic and autoimmune diseases in AA, thereby better understanding its pathogenesis. Methods A total of 4334 patients with AA were identified from the National Health Insurance Database in Taiwan from 1996 to 2008. A national representative cohort of 784,158 persons served as control subjects. Results Among patients with AA, there were significant associations with vitiligo, lupus erythematosus, psoriasis, atopic dermatitis, autoimmune thyroid disease, and allergic rhinitis. Different Ages at Onset resulted in disparate comorbidities. Increased risk of atopic dermatitis (odds ratio [OR] 3.82, 95% confidence interval 2.67-5.45) and lupus erythematosus (OR 9.76, 95% confidence interval 3.05-31.21) were found in childhood AA younger than 10 years. Additional diseases including psoriasis (OR 2.43) and rheumatoid arthritis (OR 2.57) appeared at Onset Age 11 to 20 years. Most atopic and autoimmune diseases were observed at Onset Ages of 21 to 60 years. With Onset Age older than 60 years, thyroid disease (OR 2.52) was highly related to AA. Moreover, patients with AA had higher risk for more coexisting diseases than control subjects. Limitations We could not differentiate hypothyroidism from hyperthyroidism. Conclusions AA is related to various atopic and autoimmune diseases. Different associated diseases in each Onset Age group of AA can allow clinician to efficiently investigate specific comorbidities.
Marc Cruts - One of the best experts on this subject based on the ideXlab platform.
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estimation of the genetic contribution of presenilin 1 and 2 mutations in a population based study of presenile alzheimer disease
Human Molecular Genetics, 1998Co-Authors: Marc Cruts, Marleen Van Den Broeck, John Hardy, H Backhovens, Cornelia M Van Duijn, A Wehnert, Sally Serneels, R Sherrington, Mike Hutton, Peter St GeorgehyslopAbstract:Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with Onset Age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkAge analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in Onset Ages above 55 years, with one segregating in an autosomal dominant family with mean Onset Age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with Onset Age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.
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molecular genetic analysis of familial early Onset alzheimer s disease linked to chromosome 14q24 3
Human Molecular Genetics, 1995Co-Authors: Marc Cruts, H Backhovens, A Wehnert, Shengyue Wang, G Van Gassen, Jessie Theuns, C De Jonghe, J De Voecht, G De Winter, Patrick CrasAbstract:Genetic linkAge studies have indicated that chromosome 14q24.3 harbours a major locus for early-Onset (Onset Age <65 years) Alzheimer's disease (AD3). Positional cloning efforts have identified a novel gene S182 or presenilin 1 as the AD3 gene. We have mapped S182 in the AD3 candidate region between D14S277 and D14S284 defined by genetic linkAge studies in the two chromosome 14 linked, early-Onset AD families AD/A and AD/B. We have shown that S182 is expressed in lymphoblasts and have determined the complete cDNA in both brain and lymphoblasts by RT-PCR sequencing. S182 is alternatively spliced in both brain and lymphoblasts within a putative phosphorylation site located 5' in the coding region. We identified two novel mutations, lle143Thr and Gly384Ala located in, respectively, the second transmembrane domain and in the sixth hydrophilic loop of the putative transmembrane structure of S182. As families AD/A and AD/B have a very similar AD phenotype our observation of two mutations in functionally different domains suggest that Onset Age and severity of AD may not be very helpful predictors of the location of putative S182 mutations.
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apoe genotype does not modulate Age of Onset in families with chromosome 14 encoded alzheimer s disease
Neuroscience Letters, 1994Co-Authors: Christine Van Broeckhoven, H Backhovens, Marc Cruts, Jean Jacques Martin, Richard Crook, H Houlden, John HardyAbstract:Abstract A recent study has demonstrated an association of the apolipoprotein E allele ɛ4 (APOE*4) to familial and sporadic late-Onset Alzheimer's disease (AD). Also, in late-Onset AD families linked to chromosome 19, the Onset Age decreased when the number of APOE*4 alleles increased. A similar effect of the APOE*4 genotype was observed in early-Onset AD families linked to mutations in the APP gene located on chromosome 21. We assessed whether the APOE genotype had an influence on the Age of Onset of AD in chromosome 14 linked early-Onset AD families. No significant effect of the APOE genotype on Onset Age could be detected.
H Backhovens - One of the best experts on this subject based on the ideXlab platform.
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estimation of the genetic contribution of presenilin 1 and 2 mutations in a population based study of presenile alzheimer disease
Human Molecular Genetics, 1998Co-Authors: Marc Cruts, Marleen Van Den Broeck, John Hardy, H Backhovens, Cornelia M Van Duijn, A Wehnert, Sally Serneels, R Sherrington, Mike Hutton, Peter St GeorgehyslopAbstract:Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with Onset Age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkAge analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in Onset Ages above 55 years, with one segregating in an autosomal dominant family with mean Onset Age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with Onset Age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.
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molecular genetic analysis of familial early Onset alzheimer s disease linked to chromosome 14q24 3
Human Molecular Genetics, 1995Co-Authors: Marc Cruts, H Backhovens, A Wehnert, Shengyue Wang, G Van Gassen, Jessie Theuns, C De Jonghe, J De Voecht, G De Winter, Patrick CrasAbstract:Genetic linkAge studies have indicated that chromosome 14q24.3 harbours a major locus for early-Onset (Onset Age <65 years) Alzheimer's disease (AD3). Positional cloning efforts have identified a novel gene S182 or presenilin 1 as the AD3 gene. We have mapped S182 in the AD3 candidate region between D14S277 and D14S284 defined by genetic linkAge studies in the two chromosome 14 linked, early-Onset AD families AD/A and AD/B. We have shown that S182 is expressed in lymphoblasts and have determined the complete cDNA in both brain and lymphoblasts by RT-PCR sequencing. S182 is alternatively spliced in both brain and lymphoblasts within a putative phosphorylation site located 5' in the coding region. We identified two novel mutations, lle143Thr and Gly384Ala located in, respectively, the second transmembrane domain and in the sixth hydrophilic loop of the putative transmembrane structure of S182. As families AD/A and AD/B have a very similar AD phenotype our observation of two mutations in functionally different domains suggest that Onset Age and severity of AD may not be very helpful predictors of the location of putative S182 mutations.
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apoe genotype does not modulate Age of Onset in families with chromosome 14 encoded alzheimer s disease
Neuroscience Letters, 1994Co-Authors: Christine Van Broeckhoven, H Backhovens, Marc Cruts, Jean Jacques Martin, Richard Crook, H Houlden, John HardyAbstract:Abstract A recent study has demonstrated an association of the apolipoprotein E allele ɛ4 (APOE*4) to familial and sporadic late-Onset Alzheimer's disease (AD). Also, in late-Onset AD families linked to chromosome 19, the Onset Age decreased when the number of APOE*4 alleles increased. A similar effect of the APOE*4 genotype was observed in early-Onset AD families linked to mutations in the APP gene located on chromosome 21. We assessed whether the APOE genotype had an influence on the Age of Onset of AD in chromosome 14 linked early-Onset AD families. No significant effect of the APOE genotype on Onset Age could be detected.
