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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EResearch to prevent and treat Alzheimer\u0027s disease (AD) is now focused on the development of novel therapeutic approaches that target multiple mechanisms simultaneously. Polyphenols, comprising multiple bioavailable, active metabolites, are now being studied as novel therapeutics for strategies targeting the primary and secondary prevention of AD. This article examines the effects of cocoa polyphenols in AD.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Egeriatric nutrition\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecognitive disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Edementias\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Enutrition physiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EResearch to prevent and treat Alzheimer\u0027s disease (AD) is now focused on the development of novel therapeutic approaches that target multiple mechanisms simultaneously. Polyphenols, comprising multiple bio-available, active metabolites, are now being studied as novel therapeutics for strategies targeting the primary and secondary prevention of AD. Giulio Maria Pasinetti, MD, PhD, Saunders Family Chair and Professor of Neurology, Icahn School of Medicine, Mount Sinai, New York, New York, USA, presented work from his group examining the effects of cocoa polyphenols in AD.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ESelect cocoa polyphenol metabolites promote synaptic plasticity through mechanisms that include a reduction in amyloid-\u03b2 (A\u03b2) production. At the secondary prevention level, cocoa polyphenols may decrease the burden associated with the accumulation of A\u03b2 plaques and delay the onset of cognitive impairment in individuals with AD [Sperling RA et al. \u003Cem\u003ESci Transl Med\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe primary dietary flavan-3\u2032-ol derivatives found in cocoa, as well as in grapes, are catechin, epicatechin, catechin gallate, and epicatechin gallate. In experimental studies using a transgenic mouse model of AD, the group of investigators led by Prof. Pasinetti found that grape seed-derived polyphenols are associated with improved A\u03b2 neuropathology, which, in turn, led to improved synaptic plasticity and slowed cognitive deterioration in these mice [Wang J et al. \u003Cem\u003EFront Aging Neurosci\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe effect of cocoa polyphenols on mood disorders and depression\u2014the most common psychiatric comorbidities associated with the onset and progression of AD [Pellegrino et al. \u003Cem\u003ECurr Psychiatry Rep\u003C\/em\u003E 2013]\u2014is currently being examined. Data from animal studies has been encouraging, and has shown that the reduction in depression-related immobility [Messaoudi M et al. \u003Cem\u003ENutr Neurosci\u003C\/em\u003E 2008] may be attributable to the monoamine oxidase inhibition properties of cocoa flavanols [Xu Y et al. \u003Cem\u003EPharmacol Biochem Behav\u003C\/em\u003E 2010]. Prof. Pasinetti stated that more experimental studies into AD are required to determine the role of cocoa extracts in preserving synaptic plasticity, perhaps through the attenuation of A\u03b2 conformational changes and prevention A\u03b2 neurotoxicity, to determine whether this may change the relationship between depression and AD.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe polyphenol compositions of cocoa extracts vary due to the different methods used to obtain the extracts. Natural, Dutched, and Lavado cocoa extracts have different levels of total polyphenol gallic acid equivalents and oxygen radical absorbance capacity. Prof. Pasinetti reports that Lavado cocoa was shown to prevent globin transcription factor-1 (GATA1) -mediated repression of presynaptic genes in three independent experiments (Pasinetti, data not yet published). Furthermore, Lavado cocoa extract better attenuates Ab oligomerization, followed by Natural and Dutch cocoa extracts (Wang et al. 2014 in press). In \u003Cem\u003Eex vivo\u003C\/em\u003E hippocampal slices from wild-type mice, Lavado, but not Dutch, cocoa extract prevented the impairment of long-term potentiation induced by oligomeric-Ab. Long-term potentiation is a key cellular mechanism underlying synaptic plasticity and is essential to learning and memory (Wang et al. 2014 in press).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EThe hypothetical role of cocoa flavan-3\u2032-ol metabolites in synaptic plasticity has been reviewed elsewhere [Spencer JP. \u003Cem\u003EChem Soc Rev\u003C\/em\u003E 2009]. In brief, synapse growth and increased receptor density, resulting from the activation of the CREB (cyclic adenosine monophosphate (cAMP) response element-binding protein) pathway, leads to an increase in the expression of brain-derived neurotrophic factor (BDNF), which binds to pre- and postsynaptic tyrosine kinase B (TrkB) receptors, thereby triggering glutamate release, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling, and synthesis of Arc, an immediate-early gene (IEG). PI3K and mTOR are important cellular regulatory pathways. Ongoing studies in Prof. Pasinetti\u0027s laboratory recently identified a novel role for cocoa polyphenols in influencing CREB pathways and the activation of IEGs, which are two independent but complementary molecular mechanisms influencing memory consolidation and synaptic plasticity.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EBased on the neuroprotective effects of dietary cocoa polyphenols, Prof. Pasinetti and colleagues have undertaken a multi-faceted research strategy, with the ultimate goal to accelerate translational applications in the clinical setting for the primary and secondary prevention of AD. This includes the isolation of cocoa-derived bioactive polyphenol metabolites, their structural characterization and biosynthesis, the testing of bioactive polyphenols for AD disease-modifying activity \u003Cem\u003Ein vivo\u003C\/em\u003E, and elucidation of the mechanisms of this bioactivity, including the role of molecular pathways involved in A\u03b2 generation, conformational changes, and clearance from the brain.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/5\/22.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlxi2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}