One-carbon metabolism alteration affects brain proteome profile in a mouse model of Alzheimer's disease

J Alzheimers Dis. 2010;22(4):1257-68. doi: 10.3233/JAD-2010-101107.

Abstract

Late Onset Alzheimer's Disease (LOAD) can be associated to high homocysteine level and alteration of one-carbon metabolism. We previously demonstrated in the TgCRND8 mice strain, over-expressing human amyloid-β protein precursor, that B vitamin deficiency causes alteration of one-carbon metabolism, together with unbalance of S-adenosylmethionine/S-adenosylhomocysteine levels, and is associated with AD like hallmarks as increased amyloid-β plaque deposition, hyperhomocysteinemia, and oxidative stress. The same model of nutritional deficit was used here to study the variation of the brain protein expression profile associated to B vitamin deficiency. A group of proteins mainly involved in neuronal plasticity and mitochondrial functions was identified as modulated by one-carbon metabolism. These findings are consistent with increasing data about the pivotal role of mitochondrial abnormalities in AD patho-physiology. The identified proteins might represent new potential biomarkers of LOAD to be further investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Analysis of Variance
  • Animals
  • Brain / metabolism*
  • Carbon / metabolism*
  • Cluster Analysis
  • Diet
  • Disease Models, Animal
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism
  • Oxidative Stress / physiology
  • Proteome / metabolism*
  • Vitamin B Deficiency / genetics
  • Vitamin B Deficiency / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Proteome
  • Carbon