Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice

PLoS One. 2017 Jan 19;12(1):e0170450. doi: 10.1371/journal.pone.0170450. eCollection 2017.


Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg) diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1) altered levels of amyloid precursor protein (APP) metabolites-specifically elevated amounts of β-C-terminal fragment (β-CTF) and reduced levels of solubilized amyloid Aβ40 and Aβ42 peptides; 2) reduced number and total area of amyloid plaques; 3) preserved levels of choline acetyltransferase protein (CHAT) and insulin-like growth factor II (IGF2) and 4) absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.

MeSH terms

  • Alzheimer Disease / diet therapy
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloidosis / pathology
  • Amyloidosis / prevention & control*
  • Animals
  • Animals, Newborn
  • Choline / administration & dosage*
  • Choline O-Acetyltransferase / metabolism*
  • Dietary Supplements*
  • Disease Models, Animal
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Neurogenesis / drug effects
  • Pregnancy
  • Presenilin-1 / genetics*
  • Presenilin-1 / metabolism


  • Amyloid beta-Protein Precursor
  • Mutant Proteins
  • Presenilin-1
  • presenilin 1, mouse
  • Choline O-Acetyltransferase
  • Choline