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Arch Neurol. 2005 Dec;62(12):1821-30.

Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life.

Author information

1
Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA. sniderj@neuro.wustl.edu

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, AND PARTICIPANTS:

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.

PMID:
16344340
DOI:
10.1001/archneur.62.12.1821
[Indexed for MEDLINE]
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