title: Cerebrospinal fluid biomarkers in Alzheimer's disease families with PSEN1 mutations.
abstract: OBJECTIVE
  Familial Alzheimer's disease allows studies in the preclinical phases of the disease. We studied cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42), total tau (t-tau) and phospho-tau181 (p-tau) levels in PSEN1 families and correlated the results with the genetic status, age and clinical stage.
  
  
  METHODS
  Thirteen subjects from 3 families with 2 PSEN1 mutations (L286P, M139T) were recruited from the genetic counseling program for familial dementia. Eight mutation carriers (MC) and 5 noncarriers (NC) underwent clinical and cognitive evaluations. CSF concentrations were obtained by ELISA methodology.
  
  
  RESULTS
  Symptomatic MC presented reduced CSF Aβ1-42 (mean = 175 pg/ml) and elevated t-tau (mean = 635 pg/ml) compared to controls, but not asymptomatic MC (mean = 684 and 255 pg/ml, respectively) at a median of -12.8 years from the predicted disease onset (adjusted age). Aβ1-42 levels presented an inverse correlation with the adjusted age (r = -1, p < 0. 01) in asymptomatic MC, but not in symptomatic MC or NC. t-tau presented a trend towards a negative correlation with Mini Mental State Examination (MMSE; r = -0.949, p = 0.051) in symptomatic MC but not in asymptomatic MC. In the whole group of MC, t-tau presented a significant positive correlation with Clinical Dementia Rating sum of boxes (r = 0.913, p = 0.002) and a negative correlation with MMSE (r = -0.946, p < 0.001).
  
  
  CONCLUSIONS
  CSF Aβ1-42 levels correlate with time to disease onset in asymptomatic MC to reach floor levels when symptoms appear. CSF t-tau levels become elevated in symptomatic MC and correlate with clinical severity. These findings may suggest that the changes in Aβ1-42 precede t-tau elevation in PSEN1 MC.
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bosch
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.forename: Rafael
authors.initials: R
authors.lastname: Oliva
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics*; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins