Grape Seed Compound Slows Progression of Alzheimer’s Disease in Mouse Model

A team of neurobiologists has identified the specific polyphenolic compound responsible for improved cognitive function in a mouse model of Alzheimer's disease (AD).

Investigators at Mount Sinai School of Medicine (New York, NY, USA) had previously shown that compounds present in grape seed polyphenolic extract (GSPE) protected against the development of Alzheimer’s disease by blocking the formation of toxic amyloid-beta (A-beta) oligomers in brain tissue.

In the current study, which was published in the April 11, 2012, issue of the Journal of Neuroscience, they revealed new information relating to the bioavailability, metabolism, and bioactivity of this compound, especially in the brain.

They reported that GSPE is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric forms. Following oral administration of the independent GSPE forms, only Mo was able to improve cognitive function and only Mo metabolites could selectively reach and accumulate in the brain. Furthermore, they showed that a biosynthetic epicatechin metabolite, 3′-O-methyl-epicatechin-5-O-beta-glucuronide (3′-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promoted basal synaptic transmission and long-term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. This activity benefited cognition by improving synaptic plasticity in the brain.

“My team, along with many members of the scientific community, did not know how we could harness the efficacy of naturally occurring polyphenols in food for treatment of Alzheimer’s disease,” said senior author Dr. Giulio Maria Pasinetti, professor of neurology at Mount Sinai School of Medicine. “We were skeptical that these naturally occurring polyphenols would reach the brain because they are extensively metabolized following ingestion. While this is an exciting development, we have a lot to discover and many years of testing before this agent can be considered in humans. I look forward to further studying this compound to determine its feasibility as a treatment for Alzheimer’s disease.”

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