title: Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation.
abstract: OBJECTIVE
  Aggregation and deposition of amyloid beta (Abeta) in the brain is thought to be central to the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that cerebrospinal fluid (CSF) Abeta levels are strongly correlated with AD status and progression, and may be a meaningful endophenotype for AD. Mutations in presenilin 1 (PSEN1) are known to cause AD and change Abeta levels. In this study, we have investigated DNA sequence variation in the presenilin (PSEN1) gene using CSF Abeta levels as an endophenotype for AD.
  
  
  METHODS
  We sequenced the exons and flanking intronic regions of PSEN1 in clinically characterized research subjects with extreme values of CSF Abeta levels.
  
  
  RESULTS
  This novel approach led directly to the identification of a disease-causing mutation in a family with late-onset AD.
  
  
  CONCLUSIONS
  This finding suggests that CSF Abeta may be a useful endophenotype for genetic studies of AD. Our results also suggest that PSEN1 mutations can cause AD with a large range in age of onset, spanning both early- and late-onset AD.
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors: John S K
authors: JS
authors: Kauwe
authors: Sarah
authors: S
authors: Jacquart
authors: Sumi
authors: S
authors: Chakraverty
authors: Jun
authors: J
authors: Wang
authors: Kevin
authors: K
authors: Mayo
authors: Anne M
authors: AM
authors: Fagan
authors: David M
authors: DM
authors: Holtzman
authors: John C
authors: JC
authors: Morris
authors: Alison M
authors: AM
authors: Goate
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009483:Neuropsychological Tests; D010957:Plasmids / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1