title: Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD.
  
  
  METHODS
  We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing.
  
  
  RESULTS
  When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01).
  
  
  CONCLUSIONS
  The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD.
authors.affiliation: National Institute of Mental Health, Geriatric Psychiatry Branch, Building 10, Room 3N228, 9000 Rockville Pike, Bethesda, MD 20892, USA. trey@mail.nih.gov
authors.forename: Trey
authors.initials: T
authors.lastname: Sunderland
authors.forename: Nadeem
authors.initials: N
authors.lastname: Mirza
authors.forename: Karen T
authors.initials: KT
authors.lastname: Putnam
authors.forename: Gary
authors.initials: G
authors.lastname: Linker
authors.forename: Deepa
authors.initials: D
authors.lastname: Bhupali
authors.forename: Rob
authors.initials: R
authors.lastname: Durham
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
authors.forename: Lida
authors.initials: L
authors.lastname: Kimmel
authors.forename: David
authors.initials: D
authors.lastname: Friedman
authors.forename: Judy
authors.initials: J
authors.lastname: Bergeson
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Csako
authors.forename: James A
authors.initials: JA
authors.lastname: Levy
authors.forename: John J
authors.initials: JJ
authors.lastname: Bartko
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000453:epidemiology / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016009:Chi-Square Distribution; D003710:Demography; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012306:Risk; D013129:Spinal Puncture / Q000379:methods; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins