Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-ß42 to amyloid-ß40 ratio.
Neurobiol Aging
; 35(11): 2657.e1-2657.e6, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25018108
ABSTRACT
Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.6 ± 7.7 years (n = 5; range, 40-58 years). By using genetic analysis of 3 collected patients' DNA samples, we identified a heterozygous APP gene mutation (g.275363A>T, K724M according to APP770). Finally, when APP695 with K724M mutation was ectopically expressed in HEK293 cell, the ratio of amyloid-ß42 to amyloid-ß40 was 2.23-fold higher than that of wild-type control. Together, our data suggest that APP K724M gene mutation may contribute to the cause of this Chinese early-onset familial AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Precursor de Proteína beta-Amiloide
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Povo Asiático
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Estudos de Associação Genética
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Doença de Alzheimer
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Mutação
Tipo de estudo:
Etiology_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article