Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology

Laurent, Cyril; Eddarkaoui, Sabiha; Derisbourg, Maxime; Leboucher, Antoine; Demeyer, Dominique; Carrier, Sébastien; Schneider, Marion; Hamdane, Malika; Müller, Christian; Buée, Luc; Blum, David

doi:10.1016/j.neurobiolaging.2014.03.027

Cited by 166 publications

(119 citation statements)

References 81 publications

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

“…In addition, caffeine treatment significantly reduces hippocampal tau phosphorylation and the respective proteolytic tau fragments in THY-Tau22 mice (Laurent et al, 2014). Caffeine-treated THY-Tau22 mice also exhibit improved spatial memory performance in the Morris Water Maze test (Laurent et al, 2014). The anti-oxidative effect of caffeine has also been demonstrated to be associated with the decrease of Aβ and phosphorylated tau in the cholesterol-induced sporadic AD model in rabbits (Prasanthi et al, 2010).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

“…In THY-Tau22 transgenic mice, whose markers of innate immunity (e.g., CD68, CD45, and toll-like receptor 2), several proinflammatory cytokines (e.g., CCL4, CCL5, and TNF-α), and the astrocytic marker GFAP are significantly higher in the hippocampus than those in wild-type animals, caffeine treatment significantly decreases the mRNA levels of CD45, toll-like receptor 2, CCL4, and TNF-α (Laurent et al, 2014). As evidence of its potent anti-oxidative effects, caffeine can M A N U S C R I P T…”

Section: Caffeinementioning

confidence: 98%

“…20 scavenge OH and OCH3 free radicals (Leon-Carmona and Galano, 2011) as well as suppress the mRNA levels of several oxidative stress markers in THY-Tau22 mice (Laurent et al, 2014). In addition, caffeine treatment significantly reduces hippocampal tau phosphorylation and the respective proteolytic tau fragments in THY-Tau22 mice (Laurent et al, 2014).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

See 3 more Smart Citations

Plant alkaloids as drug leads for Alzheimer's disease

2015

Neurochemistry International

178

114

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

Section: Caffeinementioning

confidence: 98%

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

See 2 more Smart Citations

Plant alkaloids as drug leads for Alzheimer's disease

2015

Neurochemistry International

178

114

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“…Human epidemiological and animal experimentation studies as well as studies conducted in cultured cell models have shown that caffeine protects against the onset and severity of AD [19][20][21][22][23][24][25][26][27][28]. Additionally, it has been shown that it can reverse behavioral and pathological features of AD [19,21,22,24,25,[29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Caffeine blocks cholesterol-enriched diet induced AD-like pathology in rabbits

Chen¹,

Tian²,

Ghribi³

et al. 2016

J Integr Syst Neurosci

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The pathogenesis of sporadic AD is believed to result from complex interactions between nutritional, environmental, epigenetic and genetic factors. Among those factors, elevated plasma cholesterol, independent of APOE genotypes, is strongly linked to the pathogenesis of sporadic AD, whereas chronic ingestion of caffeine is protective against sporadic AD. Others and we have shown that rabbits-fed cholesterol-enriched diet exhibit early AD-like pathological features including bloodbrain barrier (BBB) leakage and endolysosome dysfunction, as well as, AD-like pathological hallmarks including synaptic disruption, increased intraneuronal and brain deposition of amyloid beta (Aβ), and tau pathology. Further, we found that caffeine protects against the cholesterol-induced increases in BBB permeability. Here, we determined the extent to which caffeine affects cholesterol-enriched diet-induced increases in other pathological features of AD. We demonstrated that caffeine administration at low and moderate doses did not affect plasma levels of cholesterol, but did block significantly cholesterol-enriched diet-induced increases in brain levels of apoB and accumulation of apoB in neuronal endolysosomes. Furthermore, we demonstrated that caffeine administration at the two doses blocked cholesterol-enriched diet-induced abnormal accumulation of synaptophysin, Aβ, and phosphorylated tau in endolysosomes. Our findings suggest that caffeine exerts its protective effects against the development of sporadic AD-like pathological features, in part, by preventing the entrance of LDL cholesterol into brain parenchyma, the accumulation of LDL-cholesterol in neuronal endolysosomes, and structural and functional changes to endolysosomes.

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