Clinical, imaging, pathological, and biochemical characterization of a novel presenilin 1 mutation (N135Y) causing Alzheimer's disease.
Neurobiol Aging
; 49: 216.e7-216.e13, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-27793474
ABSTRACT
We present 2 cases of early-onset Alzheimer's disease due to a novel N135Y mutation in PSEN1. The proband presented with memory and other cognitive symptoms at age 32. Detailed clinical characterization revealed initial deficits in memory with associated dysarthria, progressing to involve executive dysfunction, spastic gait, and episodic confusion with polyspike discharges on long-term electroencephalography. Amyloid- and FDG-PET scans showed typical results of Alzheimer's disease. By history, the proband's father had developed cognitive symptoms at age 42 and died at age 48. Neuropathological evaluation confirmed Alzheimer's disease, with moderate to severe amyloid angiopathy. Skeletal muscle showed type 2 fiber-predominant atrophy with pale central clearing. Genetic testing of the proband revealed an N135Y missense mutation in PSEN1. This mutation was predicted to be pathogenic by in silico analysis. Biochemical analysis confirmed that the mutation caused an increased Aß42/Aß40 ratio, consistent with other PSEN1 mutations and with a loss of presenilin function.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Presenilina-1
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Estudios de Asociación Genética
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Enfermedad de Alzheimer
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Neuroimagen
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Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Neurobiol Aging
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos