PubMed:17502474 JSONTXT

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":17,"end":29},"obj":"gene:5663"},{"id":"T1","span":{"begin":58,"end":75},"obj":"disease:C0002395"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.\nOBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.\nDESIGN: Description of a novel phenotype associated with a presenilin 1 mutation.\nSETTING: The subject was an outpatient who was diagnosed at the local referral center.\nPATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected.\nMAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue.\nRESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42.\nCONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":139,"end":156},"obj":"HP_0002511"}],"text":"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.\nOBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.\nDESIGN: Description of a novel phenotype associated with a presenilin 1 mutation.\nSETTING: The subject was an outpatient who was diagnosed at the local referral center.\nPATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected.\nMAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue.\nRESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42.\nCONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition."}

{"project":"DisGeNET5_variant_disease","denotations":[{"id":"17502474-0#30#35#geners63750577","span":{"begin":681,"end":692},"obj":"geners63750577"},{"id":"17502474-0#58#75#diseaseC0002395","span":{"begin":1139,"end":1245},"obj":"diseaseC0002395"},{"id":"17502474-8#10#15#geners63750577","span":{"begin":867,"end":872},"obj":"geners63750577"},{"id":"17502474-8#68#73#diseaseC0002726","span":{"begin":925,"end":930},"obj":"diseaseC0002726"},{"id":"17502474-8#82#87#diseaseC0002726","span":{"begin":939,"end":944},"obj":"diseaseC0002726"},{"id":"17502474-8#131#136#diseaseC0002726","span":{"begin":988,"end":993},"obj":"diseaseC0002726"}],"relations":[{"id":"30#35#geners6375057758#75#diseaseC0002395","pred":"associated_with","subj":"17502474-0#30#35#geners63750577","obj":"17502474-0#58#75#diseaseC0002395"},{"id":"10#15#geners6375057768#73#diseaseC0002726","pred":"associated_with","subj":"17502474-8#10#15#geners63750577","obj":"17502474-8#68#73#diseaseC0002726"},{"id":"10#15#geners6375057782#87#diseaseC0002726","pred":"associated_with","subj":"17502474-8#10#15#geners63750577","obj":"17502474-8#82#87#diseaseC0002726"},{"id":"10#15#geners63750577131#136#diseaseC0002726","pred":"associated_with","subj":"17502474-8#10#15#geners63750577","obj":"17502474-8#131#136#diseaseC0002726"}],"text":"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.\nOBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.\nDESIGN: Description of a novel phenotype associated with a presenilin 1 mutation.\nSETTING: The subject was an outpatient who was diagnosed at the local referral center.\nPATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected.\nMAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue.\nRESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42.\nCONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"17502474-0#17#29#gene5663","span":{"begin":661,"end":673},"obj":"gene5663"},{"id":"17502474-0#58#75#diseaseC0002395","span":{"begin":1139,"end":1245},"obj":"diseaseC0002395"},{"id":"17502474-10#138#143#gene5663","span":{"begin":1338,"end":1343},"obj":"gene5663"},{"id":"17502474-10#177#182#diseaseC0002726","span":{"begin":1377,"end":1382},"obj":"diseaseC0002726"}],"relations":[{"id":"17#29#gene566358#75#diseaseC0002395","pred":"associated_with","subj":"17502474-0#17#29#gene5663","obj":"17502474-0#58#75#diseaseC0002395"},{"id":"138#143#gene5663177#182#diseaseC0002726","pred":"associated_with","subj":"17502474-10#138#143#gene5663","obj":"17502474-10#177#182#diseaseC0002726"}],"text":"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.\nOBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.\nDESIGN: Description of a novel phenotype associated with a presenilin 1 mutation.\nSETTING: The subject was an outpatient who was diagnosed at the local referral center.\nPATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected.\nMAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue.\nRESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42.\nCONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition."}

{"project":"PubCasesHPO","denotations":[{"id":"AB1","span":{"begin":139,"end":156},"obj":"HP:0002511"},{"id":"TI1","span":{"begin":58,"end":75},"obj":"HP:0002511"},{"id":"AB2","span":{"begin":544,"end":567},"obj":"HP:0002185"},{"id":"AB3","span":{"begin":1228,"end":1245},"obj":"HP:0002511"}],"text":"Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.\nOBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.\nDESIGN: Description of a novel phenotype associated with a presenilin 1 mutation.\nSETTING: The subject was an outpatient who was diagnosed at the local referral center.\nPATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected.\nMAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue.\nRESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42.\nCONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition."}