Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice

J Alzheimers Dis. 2018;64(1):249-267. doi: 10.3233/JAD-170880.


We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.

Keywords: Alzheimer’s disease; behavioral impairments; metabolomics; pre-emptive medicine; tocotrienol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Antioxidants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism*
  • Cues
  • Disease Models, Animal
  • Male
  • Maze Learning / drug effects
  • Mental Disorders / drug therapy*
  • Mental Disorders / etiology
  • Metabolic Networks and Pathways / drug effects*
  • Metabolic Networks and Pathways / physiology
  • Metabolomics / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Palm Oil / chemistry*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Recognition, Psychology / drug effects
  • Spatial Navigation / drug effects
  • Statistics, Nonparametric
  • Time Factors
  • Tocotrienols / therapeutic use*


  • Amyloid beta-Protein Precursor
  • Antioxidants
  • Presenilin-1
  • Tocotrienols
  • Palm Oil