Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life.
Arch Neurol
; 62(12): 1821-30, 2005 Dec.
Article
em En
| MEDLINE
| ID: mdl-16344340
ABSTRACT
BACKGROUND:
Cases of early-onset Alzheimer disease (AD) with an autosomal dominant inheritance pattern (familial AD [FAD]) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We describe herein a kindred with very early-onset FAD (age, <40 years) with unusual pathological features and a novel mutation in the presenilin 1 (PSEN1) gene (S170F) and review the existing literature on very early-onset FAD.OBJECTIVE:
To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life. DESIGN, SETTING, ANDPARTICIPANTS:
The proband underwent full clinical assessment and postmortem examination at the Washington University Alzheimer's Disease Research Center, St Louis, Mo. Limited pathological samples and autopsy records of 2 affected family members were available. The proband underwent screening for mutations in genes linked with FAD.RESULTS:
Dementia developed in 3 family members in this kindred at a mean age of 27 years; the proband had myoclonus, seizures, and rigidity, similar to findings in previously described kindreds with PSEN1 mutations. All 3 family members were confirmed to have AD by neuropathological examination. The proband also had widespread Lewy body pathology in the brainstem, limbic areas, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. The proband had a single mutation (S170F) in exon 6 of the PSEN1 gene, which segregates with disease.CONCLUSIONS:
A novel PSEN1 mutation causes very-early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies.
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Base de dados:
MEDLINE
Assunto principal:
Corpos de Lewy
/
Predisposição Genética para Doença
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Doença por Corpos de Lewy
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Doença de Alzheimer
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Proteínas de Membrana
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Mutação
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article