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Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life.
- Source :
-
Archives of neurology [Arch Neurol] 2005 Dec; Vol. 62 (12), pp. 1821-30. - Publication Year :
- 2005
-
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.<br />Objective: To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Age of Onset
Alzheimer Disease pathology
Alzheimer Disease physiopathology
Amino Acid Substitution genetics
Brain metabolism
Brain pathology
Brain physiopathology
Chromosome Disorders genetics
Chromosome Disorders pathology
Chromosome Disorders physiopathology
Disease Progression
Exons genetics
Family Health
Fatal Outcome
Female
Humans
Lewy Bodies metabolism
Lewy Body Disease pathology
Lewy Body Disease physiopathology
Male
Neurofibrillary Tangles genetics
Neurofibrillary Tangles metabolism
Neurofibrillary Tangles pathology
Pedigree
Plaque, Amyloid genetics
Plaque, Amyloid metabolism
Plaque, Amyloid pathology
Presenilin-1
alpha-Synuclein genetics
alpha-Synuclein metabolism
Alzheimer Disease genetics
Genetic Predisposition to Disease genetics
Lewy Bodies genetics
Lewy Body Disease genetics
Membrane Proteins genetics
Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9942
- Volume :
- 62
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Archives of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 16344340
- Full Text :
- https://doi.org/10.1001/archneur.62.12.1821