The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.

ABSTRACT: Apolipoprotein E (APOE) ?4 and low cerebrospinal fluid (CSF) amyloid-?42 (A?42) 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 ?4 genotype and low CSF A?42 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 A?42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline A?42 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 A?42 tertiles or ?4 status. After 18 months of DHA supplementation, participants at the lowest A?42 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 A?42 levels were significantly lower in ?4 carriers than in ?4 noncarriers (p?=?0.01). Participants carrying the ?4 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 ?4 allele and lower CSF A?42 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.

SUBMITTER: Yassine HN 

PROVIDER: S-EPMC4928349 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature