title: Clinical characterization of a presenilin 1 mutation (F177S) in a family with very early-onset Alzheimer's disease in the third decade of life.
abstract: BACKGROUND
  Early-onset familial Alzheimer disease (AD) is an autosomal dominant disorder caused by mutations in the amyloid precursor protein, presenilin 1 (PSEN1), or presenilin 2 gene. The objective of this study was to characterize the phenotype in a large family with a PSEN1 F177S mutation by performing detailed clinical assessments, neuroimaging, and neuropathological analysis.
  
  
  METHODS
  In two subjects, clinical and neuropsychological assessments, structural magnetic resonance imaging, F-18-2-fluoro-2-deoxy-D-glucose positron emission tomographic imaging, AD biomarkers in cerebrospinal fluid and genetic analysis were available. In three deceased affected subjects, medical records were reviewed. In one subject, a complete neuropathological examination was available.
  
  
  RESULTS
  Cognitive impairment and neurological symptoms developed homogeneously around 30 years of age and worsened rapidly. All subjects died about 7 years (range, 6-8 years) after disease onset before 40 years of age. All technical diagnostic information (neuroimaging, cerebrospinal fluid) were typically for AD. Neuropathology showed abundant neuritic plaques and neurofibrillary tangles, typical of severe AD. Antidementia treatment in one subject did not alter the length of survival.
  
  
  CONCLUSIONS
  The PSEN1 F177S mutation leads to typical AD starting at age 30 and a homogeneous phenotype with rapid cognitive decline and prominent neurological symptoms. Excessive amyloid beta 42 production in the brain cortex corresponds well with other PSEN1 mutations.
authors.affiliation: Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Hausner
authors.affiliation: Department of Neurodegeneration and Neurobiology, Saarland University, Saarbrueckken, Germany; Department of Neurology, Saarland University, Saarbrueckken, Germany.
authors.forename: Jakob A
authors.initials: JA
authors.lastname: Tschäpe
authors.affiliation: Department of Neuropathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Schmitt
authors.affiliation: Department of Neuroradiology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hentschel
authors.affiliation: Department of Neurodegeneration and Neurobiology, Saarland University, Saarbrueckken, Germany; Department of Neurology, Saarland University, Saarbrueckken, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.affiliation: Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany. Electronic address: lutz.froelich@zi-mannheim.de.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D058256:Brain Waves / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004569:Electroencephalography; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010649:Phenylalanine / Q000235:genetics; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics*; D011859:Radiography; D012694:Serine / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D012694:Serine; D010649:Phenylalanine
keywords: Early-onset Alzheimer's disease; Genetics; Mutation; Neuropathology; PSEN1; Phenotype