title: Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease.
abstract: OBJECTIVE
  Biological markers of utility in tracking Alzheimer's disease (AD) during the presymptomatic prodromal phase are important for prevention studies. Changes in cerebrospinal fluid (CSF) levels of 42-amino-acid β-amyloid (Aβ(42)), total tau protein (t-tau) and phosphorylated tau at residue 181 (p-tau(181)) during this state are incompletely characterized.
  
  
  METHODS
  We measured CSF markers in 13 carriers of familial AD (FAD) mutations that are fully penetrant for causing AD (PSEN1 and APP) and in 5 non-mutation-carrying family members.
  
  
  RESULTS
  Even among the entirely presymptomatic mutation carriers (n = 9), Aβ(42) was diminished (388.7 vs. 618.4 pg/ml, p = 0.004), and t-tau (138.5 vs. 50.5 pg/ml, p = 0.002) and p-tau(181) (71.7 vs. 24.6 pg/ml, p = 0.003) were elevated. There was a negative correlation between Aβ(42) levels and age relative to the family-specific age of dementia diagnosis.
  
  
  CONCLUSIONS
  Our data are consistent with a decline in CSF Aβ(42) levels occurring at least 20 years prior to clinical dementia in FAD.
authors.affiliation: Mary S. Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, Calif., USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Yaneth
authors.initials: Y
authors.lastname: Rodriguez-Agudelo
authors.forename: Luis D
authors.initials: LD
authors.lastname: Medina
authors.forename: Karen
authors.initials: K
authors.lastname: Gylys
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cummings
authors.forename: Greg M
authors.initials: GM
authors.lastname: Cole
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D042241:Early Diagnosis; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D015415:Biomarkers; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D004247:DNA