The Experts below are selected from a list of 3381 Experts worldwide ranked by ideXlab platform
Jean Jacques Martin - One of the best experts on this subject based on the ideXlab platform.
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Presenile Dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β amyloid precursor protein gene
Nature Genetics, 1992Co-Authors: Lydia Hendriks, Cornelia M Van Duijn, Patrick Cras, Marc Cruts, Wim Van Hul, Frans Van Harskamp, Andrew C Warren, Melvin G Mcinnis, Stylianos E Antonarakis, Jean Jacques MartinAbstract:Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with Presenile Dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, Presenile Dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.
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Presenile Dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein gene
Nature Genetics, 1992Co-Authors: Lydia Hendriks, Cornelia M Van Duijn, Patrick Cras, Marc Cruts, Wim Van Hul, Frans Van Harskamp, Andrew C Warren, Melvin G Mcinnis, Stylianos E Antonarakis, Jean Jacques MartinAbstract:Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with Presenile Dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, Presenile Dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.
Michel Goedert - One of the best experts on this subject based on the ideXlab platform.
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Mutation in the tau gene in familial multiple system tauopathy with Presenile Dementia
Proceedings of the National Academy of Sciences, 1998Co-Authors: Maria Grazia Spillantini, Michel Goedert, J Illr . Murrell, Martin R Farlow, Aaron Klug, Bernardino GhettiAbstract:Familial multiple system tauopathy with Presenile Dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal Dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3′ neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer’s disease and other tauopathies.
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familial multiple system tauopathy with Presenile Dementia is localized to chromosome 17
American Journal of Human Genetics, 1997Co-Authors: J Illr . Murrell, Maria Grazia Spillantini, Michel Goedert, Daniel L Koller, Tatiana Foroud, Howard J Edenberg, Martin R Farlow, Bernardino GhettiAbstract:Summary An autosomal dominant Presenile Dementia affecting 39 individuals in a seven-generation, 383-member pedigree has been studied at Indiana University. In the affected members of this family, clinical symptoms occurred early in life, with an average age at onset of 48.8 years. The presenting clinical features include disequilibrium, neck stiffness, dysphagia, and memory loss. As the disease progresses, further cognitive decline, superior-gaze palsy, and dystaxia also are observed. The average duration from onset of symptoms to death is ∼10 years. Neuropathologic studies of nine affected individuals showed neuronal loss in several areas of the CNS, as well as argentophilic tau-immunopositive inclusions in neurons and in oligodendroglia. A limited genomic screen by use of DNA samples from 28 family members localized the gene for this disorder to a 3-cM region on chromosome 17, between the markers THRA1 and D17S791. The gene for tau also was analyzed, through samples from the family.
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Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial Presenile Dementia with tangles
Acta Neuropathologica, 1996Co-Authors: Maria Grazia Spillantini, R.a. Crowther, Michel GoedertAbstract:Alzheimer’s disease (AD) is characterised neuropathologically by the presence of abundant extracellular β-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of Presenile Dementia with neurofibrillary pathology and no β-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120–127]. We have compared the tau pathology in this familial form of Presenile Dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial Presenile Dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of β-amyloid deposits and that their presence is associated with Dementia.
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comparison of the neurofibrillary pathology in alzheimer s disease and familial Presenile Dementia with tangles
Acta Neuropathologica, 1996Co-Authors: Maria Grazia Spillantini, R.a. Crowther, Michel GoedertAbstract:Alzheimer’s disease (AD) is characterised neuropathologically by the presence of abundant extracellular β-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of Presenile Dementia with neurofibrillary pathology and no β-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120–127]. We have compared the tau pathology in this familial form of Presenile Dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial Presenile Dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of β-amyloid deposits and that their presence is associated with Dementia.
Maria Grazia Spillantini - One of the best experts on this subject based on the ideXlab platform.
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Mutation in the tau gene in familial multiple system tauopathy with Presenile Dementia
Proceedings of the National Academy of Sciences, 1998Co-Authors: Maria Grazia Spillantini, Michel Goedert, J Illr . Murrell, Martin R Farlow, Aaron Klug, Bernardino GhettiAbstract:Familial multiple system tauopathy with Presenile Dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal Dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3′ neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer’s disease and other tauopathies.
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familial multiple system tauopathy with Presenile Dementia is localized to chromosome 17
American Journal of Human Genetics, 1997Co-Authors: J Illr . Murrell, Maria Grazia Spillantini, Michel Goedert, Daniel L Koller, Tatiana Foroud, Howard J Edenberg, Martin R Farlow, Bernardino GhettiAbstract:Summary An autosomal dominant Presenile Dementia affecting 39 individuals in a seven-generation, 383-member pedigree has been studied at Indiana University. In the affected members of this family, clinical symptoms occurred early in life, with an average age at onset of 48.8 years. The presenting clinical features include disequilibrium, neck stiffness, dysphagia, and memory loss. As the disease progresses, further cognitive decline, superior-gaze palsy, and dystaxia also are observed. The average duration from onset of symptoms to death is ∼10 years. Neuropathologic studies of nine affected individuals showed neuronal loss in several areas of the CNS, as well as argentophilic tau-immunopositive inclusions in neurons and in oligodendroglia. A limited genomic screen by use of DNA samples from 28 family members localized the gene for this disorder to a 3-cM region on chromosome 17, between the markers THRA1 and D17S791. The gene for tau also was analyzed, through samples from the family.
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Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial Presenile Dementia with tangles
Acta Neuropathologica, 1996Co-Authors: Maria Grazia Spillantini, R.a. Crowther, Michel GoedertAbstract:Alzheimer’s disease (AD) is characterised neuropathologically by the presence of abundant extracellular β-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of Presenile Dementia with neurofibrillary pathology and no β-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120–127]. We have compared the tau pathology in this familial form of Presenile Dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial Presenile Dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of β-amyloid deposits and that their presence is associated with Dementia.
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comparison of the neurofibrillary pathology in alzheimer s disease and familial Presenile Dementia with tangles
Acta Neuropathologica, 1996Co-Authors: Maria Grazia Spillantini, R.a. Crowther, Michel GoedertAbstract:Alzheimer’s disease (AD) is characterised neuropathologically by the presence of abundant extracellular β-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of Presenile Dementia with neurofibrillary pathology and no β-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120–127]. We have compared the tau pathology in this familial form of Presenile Dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial Presenile Dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of β-amyloid deposits and that their presence is associated with Dementia.
Lydia Hendriks - One of the best experts on this subject based on the ideXlab platform.
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Presenile Dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β amyloid precursor protein gene
Nature Genetics, 1992Co-Authors: Lydia Hendriks, Cornelia M Van Duijn, Patrick Cras, Marc Cruts, Wim Van Hul, Frans Van Harskamp, Andrew C Warren, Melvin G Mcinnis, Stylianos E Antonarakis, Jean Jacques MartinAbstract:Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with Presenile Dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, Presenile Dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.
-
Presenile Dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein gene
Nature Genetics, 1992Co-Authors: Lydia Hendriks, Cornelia M Van Duijn, Patrick Cras, Marc Cruts, Wim Van Hul, Frans Van Harskamp, Andrew C Warren, Melvin G Mcinnis, Stylianos E Antonarakis, Jean Jacques MartinAbstract:Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with Presenile Dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, Presenile Dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.
Bernardino Ghetti - One of the best experts on this subject based on the ideXlab platform.
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Mutation in the tau gene in familial multiple system tauopathy with Presenile Dementia
Proceedings of the National Academy of Sciences, 1998Co-Authors: Maria Grazia Spillantini, Michel Goedert, J Illr . Murrell, Martin R Farlow, Aaron Klug, Bernardino GhettiAbstract:Familial multiple system tauopathy with Presenile Dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal Dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3′ neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer’s disease and other tauopathies.
-
familial multiple system tauopathy with Presenile Dementia is localized to chromosome 17
American Journal of Human Genetics, 1997Co-Authors: J Illr . Murrell, Maria Grazia Spillantini, Michel Goedert, Daniel L Koller, Tatiana Foroud, Howard J Edenberg, Martin R Farlow, Bernardino GhettiAbstract:Summary An autosomal dominant Presenile Dementia affecting 39 individuals in a seven-generation, 383-member pedigree has been studied at Indiana University. In the affected members of this family, clinical symptoms occurred early in life, with an average age at onset of 48.8 years. The presenting clinical features include disequilibrium, neck stiffness, dysphagia, and memory loss. As the disease progresses, further cognitive decline, superior-gaze palsy, and dystaxia also are observed. The average duration from onset of symptoms to death is ∼10 years. Neuropathologic studies of nine affected individuals showed neuronal loss in several areas of the CNS, as well as argentophilic tau-immunopositive inclusions in neurons and in oligodendroglia. A limited genomic screen by use of DNA samples from 28 family members localized the gene for this disorder to a 3-cM region on chromosome 17, between the markers THRA1 and D17S791. The gene for tau also was analyzed, through samples from the family.
