title: The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.
abstract: Apolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer's disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE ɛ4 genotype and low CSF Aβ42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial.
  
  
  
  Phospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Aβ42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Aβ42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated.
  
  
  
  At baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Aβ42 tertiles or ɛ4 status. After 18 months of DHA supplementation, participants at the lowest Aβ42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Aβ42 levels were significantly lower in ɛ4 carriers than in ɛ4 noncarriers (p = 0.01). Participants carrying the ɛ4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07).
  
  
  
  APOE ɛ4 allele and lower CSF Aβ42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD.
  
  
  
  Clinicaltrials.gov identifier: NCT00440050 . Registered on 22 Feb 2007.
authors.affiliation: Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. hyassine@usc.edu.
authors.forename: Hussein N
authors.initials: HN
authors.lastname: Yassine
authors.affiliation: Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Rawat
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.affiliation: Department of Neurology, Oregon Health & Science University, and Portland VA Medical Center , Portland, OR, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Clinical Research Department, DSM Nutritional Products, Columbia, MD, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Yurko-Mauro
authors.affiliation: Clinical Research Department, DSM Nutritional Products, Columbia, MD, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Bailey-Hall
authors.affiliation: Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Chui
authors.affiliation: Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.|Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, USA.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000178:diet therapy* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D004281:Docosahexaenoic Acids
keywords: APOE; Alzheimer’s disease; Amyloid; Cerebrospinal fluid