Editors' ChoiceAlzheimer’s Disease

Resveratrol for Alzheimer’s disease?

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Science Translational Medicine  01 Feb 2017:
Vol. 9, Issue 375, eaam6055
DOI: 10.1126/scitranslmed.aam6055

Abstract

Resveratrol modulates β-amyloid levels and inflammatory markers in patients with Alzheimer’s disease.

Resveratrol, a polyphenol found in red grapes and certain berries, has received considerable attention for its reported ability to extend life span in some model organisms and be protective in animal models of age-related disease including neurodegeneration in rodent models of Alzheimer’s disease (AD). These effects of resveratrol may be mediated through activation of the NAD-dependent protein deacetylase Sirtuin 1, which affects transcriptional regulation. Whether resveratrol has any effect on human health or aging is currently unclear and under intense investigation. Now, Moussa and colleagues provide evidence that resveratrol impacts neuroinflammation when given to patients with mild or moderate AD.

In this phase 2 clinical study, participants (n = 119) received resveratrol orally (escalating dose from 500 mg daily to 1000 mg twice daily) or placebo over a 52-week period. Resveratrol was detected in both CSF and plasma, and generally was well tolerated with some instances of adverse effects—most commonly nausea, diarrhea, and weight loss. Plasma and CSF β-amyloid (Aβ) levels are known to decline as dementia progresses; the authors report that Aβ40 declined in both CSF and plasma to a lesser extent in the resveratrol-treated group compared with the placebo group. Major findings from the current retrospective study were that CSF matrix metalloproteinase 9 (MMP9) was decreased with resveratrol treatment, whereas CSF macrophage-derived chemokine, interleukin-4, and fibroblast growth factor-2 were all increased. MMP9 is thought to influence blood-brain barrier permeability, which may be reduced in AD patients taking resveratrol. An increase in certain inflammatory markers is consistent with resveratrol possibly inducing an adaptive immune response in the CNS, which the authors hypothesize might benefit AD patients through modulating amyloid deposition. Declines in mini-mental status examination scores and activities of daily living scores were slightly attenuated with resveratrol treatment, although the study was underpowered for assessing clinical outcomes. Hence, the study generates the hypothesis that resveratrol modulates the inflammatory profile in the CNS and raises the possibility that this may be associated with mitigated cognitive and functional decline. These findings could inform larger follow-up studies with resveratrol powered to detect differences in clinical outcomes to additionally characterize the course of neuroinflammation following treatment. For now though, it remains to be determined whether resveratrol truly has any beneficial effect on AD progression and whether the promise of animal studies will translate into the clinic.

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