Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease

Gustavo Basurto-Islas, Julie Blanchard, Yunn Chyn Tung, Jose R. Fernandez, Michael Voronkov, Maxwell Stock, Sherry Zhang, Jeffry B. Stock, Khalid Iqbal

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


A minor component of coffee unrelated to caffeine, eicosanoyl-5-hydroxytryptamide (EHT), provides protection in a rat model for Alzheimer's disease (AD). In this model, viral expression of the phosphoprotein phosphatase 2A (PP2A) endogenous inhibitor, the I2PP2A, or SET protein in the brains of rats leads to several characteristic features of AD including cognitive impairment, tau hyperphosphorylation, and elevated levels of cytoplasmic amyloid-β protein. Dietary supplementation with EHT for 6-12 months resulted in substantial amelioration of all these defects. The beneficial effects of EHT could be associated with its ability to increase PP2A activity by inhibiting the demethylation of its catalytic subunit PP2Ac. These findings raise the possibility that EHT may make a substantial contribution to the apparent neuroprotective benefits associated with coffee consumption as evidenced by numerous epidemiologic studies indicating that coffee drinkers have substantially lowered risk of developing AD.

Original languageEnglish (US)
Pages (from-to)2701-2712
Number of pages12
JournalNeurobiology of Aging
Issue number12
StatePublished - Dec 1 2014

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology


  • Adenoassociated virus vector serotype 1
  • Coffee
  • Cognitive impairment
  • Eicosanoyl-5-hydroxytryptamide
  • Hyperphosphorylation of tau
  • Inhibitor-2 of protein phosphatase-2A
  • Methylation of protein phosphatase-2A
  • Protein phosphatase-2A
  • Rat model of sporadic Alzheimer's disease
  • SET
  • Tau


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