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Neurobiol Aging. 2014 Dec;35(12):2701-2712. doi: 10.1016/j.neurobiolaging.2014.06.012. Epub 2014 Jun 17.

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

Author information

1
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
2
Signum Biosciences Inc, 133 Wall Street, Princeton, NJ 08540, USA.
3
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
4
Signum Biosciences Inc, 133 Wall Street, Princeton, NJ 08540, USA; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
5
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Electronic address: khalid.iqbal.ibr@gmail.com.

Abstract

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 I2(PP2A), 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.

KEYWORDS:

Adenoassociated virus vector serotype 1; Aβ; 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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