OMIM_GOF@xiajingbo:104760-12-APP JSONTXT

{"project":"AGAC-2-2","denotations":[{"id":"T1","span":{"begin":142,"end":176},"obj":"Var"},{"id":"T10","span":{"begin":358,"end":372},"obj":"Var"},{"id":"T11","span":{"begin":387,"end":394},"obj":"NegReg"},{"id":"T12","span":{"begin":395,"end":414},"obj":"MPA"},{"id":"T13","span":{"begin":489,"end":497},"obj":"PosReg"},{"id":"T14","span":{"begin":501,"end":552},"obj":"MPA"},{"id":"T15","span":{"begin":713,"end":722},"obj":"NegReg"},{"id":"T16","span":{"begin":738,"end":758},"obj":"MPA"},{"id":"T17","span":{"begin":781,"end":790},"obj":"PosReg"},{"id":"T18","span":{"begin":791,"end":852},"obj":"MPA"},{"id":"T2","span":{"begin":101,"end":109},"obj":"Var"},{"id":"T3","span":{"begin":117,"end":120},"obj":"Gene"},{"id":"T4","span":{"begin":127,"end":139},"obj":"Reg"},{"id":"T5","span":{"begin":196,"end":201},"obj":"Var"},{"id":"T6","span":{"begin":243,"end":250},"obj":"NegReg"},{"id":"T7","span":{"begin":257,"end":274},"obj":"MPA"},{"id":"T8","span":{"begin":279,"end":288},"obj":"PosReg"},{"id":"T9","span":{"begin":293,"end":352},"obj":"MPA"}],"relations":[{"id":"R8","pred":"CauseOf","subj":"T10","obj":"T11"},{"id":"R9","pred":"ThemeOf","subj":"T12","obj":"T11"},{"id":"R1","pred":"ThemeOf","subj":"T3","obj":"T2"},{"id":"R11","pred":"ThemeOf","subj":"T14","obj":"T13"},{"id":"R12","pred":"ThemeOf","subj":"T16","obj":"T15"},{"id":"R13","pred":"ThemeOf","subj":"T18","obj":"T17"},{"id":"R2","pred":"CauseOf","subj":"T2","obj":"T4"},{"id":"R3","pred":"ThemeOf","subj":"T1","obj":"T4"},{"id":"R4","pred":"CauseOf","subj":"T5","obj":"T6"},{"id":"R5","pred":"ThemeOf","subj":"T7","obj":"T6"},{"id":"R6","pred":"CauseOf","subj":"T5","obj":"T8"},{"id":"R7","pred":"ThemeOf","subj":"T9","obj":"T8"}],"text":"\r\n\r\nIn affected members of a family with early-onset AD (104300), Ancolio et al. (1999) identified a mutation in the APP gene, resulting in a val715-to-met (V715M) substitution. Overexpression of V715M in human HEK293 cells and murine neurons reduced total A-beta production and increased the recovery of the physiologically secreted product, APP-alpha. The V715M mutation significantly reduced A-beta-40 secretion without affecting A-beta-42 production in HEK293 cells. However, a marked increase in N-terminally truncated A-beta ending at position 42 was observed, whereas its counterpart ending at position 40 was not affected. These results suggested that, in some cases, familial AD may be associated with a reduction in the overall production of A-beta, but may be caused by increased production of truncated forms of A-beta ending at position 42. This family with the V715M mutation was also reported by Campion et al. (1999), the same family having been ascertained through a population-based survey of early-onset Alzheimer disease.\r\n"}

{"project":"AGAC-2-1","denotations":[{"id":"T1","span":{"begin":142,"end":176},"obj":"Var"},{"id":"T2","span":{"begin":117,"end":120},"obj":"Gene"},{"id":"T3","span":{"begin":127,"end":139},"obj":"Reg"},{"id":"T4","span":{"begin":101,"end":109},"obj":"Var"},{"id":"T5","span":{"begin":196,"end":201},"obj":"Var"},{"id":"T6","span":{"begin":178,"end":192},"obj":"PosReg"},{"id":"T7","span":{"begin":243,"end":250},"obj":"NegReg"},{"id":"T8","span":{"begin":257,"end":274},"obj":"MPA"},{"id":"T9","span":{"begin":279,"end":288},"obj":"PosReg"},{"id":"T10","span":{"begin":293,"end":341},"obj":"MPA"},{"id":"T11","span":{"begin":358,"end":372},"obj":"Var"},{"id":"T12","span":{"begin":387,"end":394},"obj":"NegReg"},{"id":"T13","span":{"begin":395,"end":414},"obj":"MPA"},{"id":"T14","span":{"begin":489,"end":497},"obj":"PosReg"},{"id":"T15","span":{"begin":501,"end":530},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T2","obj":"T4"},{"id":"R2","pred":"CauseOf","subj":"T4","obj":"T3"},{"id":"R3","pred":"ThemeOf","subj":"T1","obj":"T3"},{"id":"R4","pred":"ThemeOf","subj":"T5","obj":"T6"},{"id":"R5","pred":"CauseOf","subj":"T6","obj":"T7"},{"id":"R6","pred":"ThemeOf","subj":"T8","obj":"T7"},{"id":"R7","pred":"CauseOf","subj":"T6","obj":"T9"},{"id":"R8","pred":"ThemeOf","subj":"T10","obj":"T9"},{"id":"R9","pred":"CauseOf","subj":"T11","obj":"T12"},{"id":"R10","pred":"ThemeOf","subj":"T13","obj":"T12"},{"id":"R11","pred":"ThemeOf","subj":"T15","obj":"T14"}],"text":"\r\n\r\nIn affected members of a family with early-onset AD (104300), Ancolio et al. (1999) identified a mutation in the APP gene, resulting in a val715-to-met (V715M) substitution. Overexpression of V715M in human HEK293 cells and murine neurons reduced total A-beta production and increased the recovery of the physiologically secreted product, APP-alpha. The V715M mutation significantly reduced A-beta-40 secretion without affecting A-beta-42 production in HEK293 cells. However, a marked increase in N-terminally truncated A-beta ending at position 42 was observed, whereas its counterpart ending at position 40 was not affected. These results suggested that, in some cases, familial AD may be associated with a reduction in the overall production of A-beta, but may be caused by increased production of truncated forms of A-beta ending at position 42. This family with the V715M mutation was also reported by Campion et al. (1999), the same family having been ascertained through a population-based survey of early-onset Alzheimer disease.\r\n"}