Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res

Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, and Department of Neurosurgery, University of South Florida, Tampa, FL 33613, USA.
Brain Research (Impact Factor: 2.84). 07/2008; 1214:177-87. DOI: 10.1016/j.brainres.2008.02.107
Source: PubMed


We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased beta-amyloid (Abeta) levels and plaques via promotion of the non-amyloidogenic alpha-secretase proteolytic pathway in "Swedish" mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces Abeta deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both Abeta1-40 and 1-42 soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial arm water maze (RAWM) testing for working memory indicated that EGCG provided cognitive benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease.

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    • "It has been shown that EGCG specifically interferes with phospholipids and proteins from plasma membrane and controls transcription factors, mitochondrial function, signal transduction pathways, DNA methylation , and autophagy [6]. Green tea exerts protective effects in arterial hypertension [7], obesity [8] [9] [10] [11], type 2 diabetes mellitus [12] [13] [14], metabolic syndrome (MetS) [15] [16] [17] [18], ischemic stroke [19], Alzheimer's disease [20] [21], Parkinson's disease [22], oral cancer [23], and breast cancer [24] [25]. In vitro, it has been extensively proven that polyphenols have anti-inflammatory activities, exerted through the modulation of enzymes and mediated by antioxidative effects. "
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    ABSTRACT: Introduction: Promising experimental and clinical trials suggest that green tea decrease inflammatory process in cardiometabolic diseases, but evidence from epidemiologic studies about the effects on plasma C-reactive protein (CRP) seems inconsistent and ambiguous. Therefore the aim of the meta-analysis was to evaluate the impact of green tea supplementation on plasma CRP concentrations. Methods: We searched selected database up to October 26, 2014 to identify randomized controlled trials (RCTs) investigating the impact of green tea supplementation on plasma CRP concentrations. Two independent reviewers extracted data on study characteristics, methods and outcomes. Results: Meta-analysis of data from 11 RCTs arms did not indicate a significant effect of supplementation with green tea catechins on plasma CRP concentrations (WMD: 0.085 mg/L, 95%CI: -0.225, 0.395, p=0.592). This effect size was robust in sensitivity analysis and omission of each individual study did not have a significant effect. The non-significant effects of green tea catechins on plasma CRP concentrations were also observed in subgroups of studies with green tea supplementation duration of <8 weeks (WMD: 0.029 mg/L, 95%CI: -0.229, 0.286, p=0.828) and ≥8 weeks (WMD: 0.099 mg/L, 95%CI: -0.555, 0.754, p=0.766). Likewise there was no significant effect in subgroups of studies with total catechins doses <400 mg/day (WMD: 0.073 mg/L, 95%CI: -0.251, 0.398, p=0.658) and ≥400 mg/day (WMD: 0.213 mg/L, 95%CI: -0.148, 0.574, p=0.247). The effect size were not significant after stratification of studies to those recruiting healthy subjects (WMD: -0.028 mg/L, 95%CI:-0.216, 0.160, p=0.769), and those recruiting subjects with cardiometabolic diseases (WMD: 0.260 mg/L, 95%CI: -0.815, 1.334, p=0.636). Conclusions: This meta-analysis of data from 11 RCT arms did not indicate a significant effect of supplementation with green tea catechins on plasma CRP concentrations. Further, well-designed trials are necessary to validate these results.
    Nutrition 02/2015; 31(9):1061–1071. DOI:10.1016/j.nut.2015.02.004 · 2.93 Impact Factor
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    • "In line with previous work [27], untreated TgCRND8 mice demonstrated poor spatial learning performance in the Barnes maze task compared to wild-type littermates, as shown by longer escape latencies and more errors. We expected the EGCG and Exercise groups to show some cognitive improvements (e.g., shorter latencies, fewer errors) based on previous research [15] [19]; however, these published studies used longer treatment periods for exercise (5–6 months), and in the case of EGCG administration, a different transgenic AD mouse model (i.e., Tg2576: [15]). In line with previous research using longer wheel running exercise durations, we found that a shorter running duration (4 months) still improved spatial learning latencies in Tg mice, compared to untreated Tg controls . "
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    ABSTRACT: Alzheimer's disease (AD) is a progressive, age-dependent neurodegenerative disorder affecting specific brain regions that control memory and cognitive functions. Epidemiological studies suggest that exercise and dietary antioxidants are beneficial in reducing AD risk. To date, botanical flavonoids are consistently associated with the prevention of age-related diseases. The present study investigated the effects of 4 months of wheel running exercise, initiated at 2-months of age, in conjunction with the effects of the green tea catechin (-)-epigallocatechin-3-gallate (EGCG) administered orally in the drinking water (50 mg/kg daily) on: 1) behavioral measures: learning and memory performance in the Barnes maze, nest building, open-field, anxiety in the light-dark box; and 2) soluble amyloid-β (Aβ) levels in the cortex and hippocampus in TgCRND8 (Tg) mice. Untreated Tg mice showed hyperactivity, relatively poor nest building behaviors, and deficits in spatial learning in the Barnes maze. Both EGCG and voluntary exercise, separately and in combination, were able to attenuate nest building and Barnes maze performance deficits. Additionally, these interventions lowered soluble Aβ1-42 levels in the cortex and hippocampus. These results, together with epidemiological and clinical studies in humans, suggest that dietary polyphenols and exercise may have beneficial effects on brain health and slow the progression of AD.
    Journal of Alzheimer's disease: JAD 10/2014; 44(2). DOI:10.3233/JAD-140981 · 4.15 Impact Factor
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    • ". The effects of flavonoids such as EGC appear to be anti-inflammatory but may also involve neuronal signaling, with effects on brain-derived neurotrophic factor (BDNF) and other factors affecting memory, learning, and cognition [80]. In transgenic AD mice, EGC reduced b-amyloid and tau aggregation [81]. Caffeine in coffee and other foods has Table 2 Summary of neuroprotective nutrients "
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    ABSTRACT: Lifestyle and health-related factors are critical components of the risk for cognitive aging among veterans. Because dementia has a prolonged prodromal phase, understanding effects across the life course could help focus the timing and duration of prevention targets. This perspective may be especially relevant for veterans and health behaviors. Military service may promote development and maintenance of healthy lifestyle behaviors, but the period directly after active duty has ended could be an important transition stage and opportunity to address some important risk factors. Targeting multiple pathways in one intervention may maximize efficiency and benefits for veterans. A recent review of modifiable risk factors for Alzheimer's disease estimated that a 25% reduction of a combination of seven modifiable risk factors including diabetes, hypertension, obesity, depression, physical inactivity, smoking, and education/cognitive inactivity could prevent up to 3 million cases worldwide and 492,000 cases in the United States. Lifestyle interventions to address cardiovascular health in veterans may serve as useful models with both physical and cognitive activity components, dietary intervention, and vascular risk factor management. Although the evidence is accumulating for lifestyle and health-related risk factors as well as military risk factors, more studies are needed to characterize these factors in veterans and to examine the potential interactions between them.
    Alzheimer's and Dementia 06/2014; 10(3):S111–S121. DOI:10.1016/j.jalz.2014.04.010 · 12.41 Impact Factor
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