Familial dementia with frontotemporal features associated with Met146Val presenilin-1 mutation

Most of the mutations in the presenilin-1 gene (PS-1) are associated with familial Alzheimer's disease (AD). However, certain examples can be associated with frontotemporal dementia (FTD). We performed a clinical evaluation of individuals belonging to a family with the FTD phenotype, and additi...

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Detalles Bibliográficos
Autores: Riudavets, Miguel Angel, Bartoloni, Leonardo, Troncoso, Juan C., Pletnikova, Olga, St. George Hyslop, Peter, Schultz, Marcelo, Sevlever, Gustavo, Allegri, Ricardo Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/25468
Acceso en línea:http://hdl.handle.net/11336/25468
Access Level:acceso abierto
Palabra clave:Frontotemporal
Alzheimer'S Disease
Presenilin 1
Pick Bodies
Ftd
M146v
Oligodendrocytes
Ps-1 Mutations
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Descripción
Sumario:Most of the mutations in the presenilin-1 gene (PS-1) are associated with familial Alzheimer's disease (AD). However, certain examples can be associated with frontotemporal dementia (FTD). We performed a clinical evaluation of individuals belonging to a family with the FTD phenotype, and additional molecular studies and neuropathological assessment of the proband. The PS-1 M146V mutation was found in the 50-year-old subject (the proband) with family history of early-onset FTD. Neuropathological examination showed abundant amyloid plaques, widespread neurofibrillary pathology, Pick bodies in the hippocampus and cortex, cortical globose tangles and ubiquitin-positive nuclear inclusions in white matter oligodendrocytes. We report a kindred with clinical features of FTD, whose proband bore the PS-1 M146V mutation and showed diffuse Alzheimer's type pathology and Pick bodies on post-mortem neuropathological examination. As with other mutations within the same codon, this substitution may predispose to both diseases by affecting APP and/or tau processing.