Mutational analysis in early-onset familial dementia in the Japanese population. The role of PSEN1 and MAPT R406W mutations.
Dement Geriatr Cogn Disord
; 26(1): 43-9, 2008.
Article
em En
| MEDLINE
| ID: mdl-18587238
ABSTRACT
BACKGROUND:
Three major causative genes have been implicated as the cause of early-onset familial Alzheimer's disease (AD) the amyloid precursor protein gene (APP), presenilin-1 (PSEN1) and PSEN2. Although rare, a tau-related dementia with mutations in the microtubule-associated protein tau gene (MAPT) has been identified in patients showing clinical presentations similar to those of AD.METHODS:
We performed mutational analysis of APP, PSEN1, PSEN2, and MAPT in 10 Japanese families with early-onset dementia clinically diagnosed as probable Alzheimer's disease.RESULTS:
In 4 index patients, we identified 4 missense PSEN1 mutations, namely, L286V, G378E, L381V, and L392V. The mean age at onset in the patients with PSEN1 mutations was 39 years. In 2 families, we found the R406W mutation in MAPT. The mean age at onset of the patients carrying the R406W mutation was 52 years, and they presented with the peculiar AD-like phenotype without apparent behavioral or language problems.CONCLUSION:
These observations suggest that although PSEN1 mutations are the most frequent cause, the MAPT R406W mutation is an important cause of early-onset familial dementia clinically diagnosed as AD. Differentiation of patients with the MAPT mutation from AD patients by genetic testing would be meaningful, considering that a different therapeutic approach should be applied.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas tau
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Demência
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Povo Asiático
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Presenilina-1
Limite:
Female
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Humans
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Male
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Middle aged
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article