A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis.
Arch Neurol
; 61(11): 1773-6, 2004 Nov.
Article
em En
| MEDLINE
| ID: mdl-15534188
BACKGROUND: Early-onset familial Alzheimer disease is caused by mutations in the amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes. Phenotypic diversity has been reported to be associated with various mutations in PSEN1. Various mutations of PSEN1 have been reported in cases of early-onset Alzheimer disease with spastic paraparesis. OBJECTIVE: To describe a novel mutation in the PSEN1 gene associated with early-onset Alzheimer disease with spastic paraparesis. PATIENT AND METHODS: The patient was a 27-year-old man who developed early-onset dementia with spastic paraparesis. We examined sequences of the PSEN1, PSEN2, and APP genes from the patient and his family. To detect a possible mutation effect on the production of amyloid-beta peptide (Abeta), transfected HEK293 cells were examined for Abeta42 and Abeta40 production. RESULTS: We found a novel mutation (Leu85Pro) in PSEN1. This mutation influenced the production of Abeta, resulting in a 2-fold elevation of Abeta42 production and of the Abeta42/40 ratio. CONCLUSION: To our knowledge, this is the first report of very early-onset Alzheimer disease with spastic paraparesis and with the visual variant form of the disease, which is associated with visuospatial cognitive disorder. The Leu85Pro mutation in PSEN1 was pathogenic.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraparesia Espástica
/
Doença de Alzheimer
/
Proteínas de Membrana
Tipo de estudo:
Etiology_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article