Folic acid potentiates the effect of memantine on spatial learning and neuronal protection in an alzheimer's disease transgenic model

Ta Fu Chen, Rwei Fen S. Huang, Sey-En Lin, Jyh Feng Lu, Ming Chi Tang, Ming Jang Chiu

Research output: Contribution to journalArticle

19 Citations (Scopus)


Folic acid deficiency and hyperhomocysteinemia potentiate amyloid-β (Aβ) neuron toxicity. Memantine, an NMDA antagonist used in moderate to severe AD, is considered to be neuroprotective. We propose that folic acid might have a synergistic effect for memantine in protecting neurons from Aβ accumulation. We treated 8-month-old Tg2576 transgenic mice with memantine (30 mg/kg/day) with or without folic acid (8 mg/kg/day) for 4 months. Escape latencies in the Morris water maze were significantly shorter in the folic acid-memantine treatment group Tg(+)-M+F compared to both the non-treatment transgenic controls Tg(+) and the memantine-treatment group Tg(+)-M (both p < 0.05). Analysis of Aβ{40} and Aβ{42} showed lower brain loads in both treatment groups but this did not reach statistical significance. Histopathology analysis showed that Tg(+)-M+F had lower ratios of neuronal damage than Tg(+) (p < 0.001) and Tg(+)-M (p< 0.005). DNA analysis revealed that in the Tg(+)M-+F group, transcription was upregulated in 72 brain genes involved in neurogenesis, neural differentiation, memory, and neurotransmission compared to the Tg(+)-M group. In conclusion, we found that folic acid may potentiate the effect of memantine on spatial learning and neuronal protection. The benefit of combination therapy may be through co-action on the methylation-controlled Aβ production, and modification of brain gene expression.

Original languageEnglish
Pages (from-to)607-615
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number2
Publication statusPublished - Jan 1 2010



  • Alzheimer's disease
  • folic acid
  • memantine
  • neuron protection
  • spatial learning
  • transgenic mice

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this