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To address the question of cross-talk between prion protein (PrP) and Alzheimer's disease (AD), we generated TgAD/GSS mice that develop amyloid-β (Aβ) plaques of AD and PrP (specifically mutated PrP A116V ) plaques of Gerstmann-Sträussler-Scheinker disease (GSS) and compared plaque-related features in these mice to AD mice that express normal (TgAD), high (TgAD/HuPrP), or no (TgAD/PrP -/- ) PrP C . In contrast to PrP C , PrP A116V weakly co-localized to Aβ plaques, did not co-immunoprecipitate with Aβ, and poorly bound to Aβ in an ELISA-based binding assay. Despite the reduced association of PrP A116V with Aβ, TgAD/GSS and TgAD/HuPrP mice that express comparable levels of PrP A116V and PrP C respectively, displayed similar increases in Aβ plaque burden and steady state levels of Aβ and its precursor APP compared with TgAD mice. Our Tg mouse lines also revealed a predominance of intracellular Aβ plaques in mice lacking PrP C (TgAD/PrP -/- , TgAD/GSS) compared with an extracellular predominance in PrP C -expressing mice (TgAD, TgAD/HuPrP). Parallel studies in N2aAPPswe cells revealed a direct dependence on PrP C but not PrP A116V for exosome-related secretion of Aβ. Overall, our findings are two-fold; they suggest that PrP expression augments Aβ plaque production, at least in part by an indirect mechanism, perhaps by increasing steady state levels of APP, while they also provide support for a fundamental role of PrP C to bind to and deliver intraneuronal Aβ to exosomes for secretion.

Alzheimer's disease is a neurodegenerative disease characterized by the production of β-amyloid proteins and hyperphosphorylation of tau protein. Inflammation and apoptotic severity were highly correlated with earlier age at onset of Alzheimer's disease and were also associated with cognitive decline. This study aims to examine whether the traditional Chinese medicine ginsennoside Rd could prevent cognitive deficit and take neuroprotective effects in β-amyloid peptide 1-40-induced rat model of Alzheimer's disease. To produce Alzheimer's disease animal model, aggregated β-amyloid peptide 1-40 injected into hippocampus bilaterally. Ginsennoside Rd protected their cognitive impairment and improved their memory function by daily intraperitoneal injection for 30 days consecutively. In addition, ginsennoside Rd alleviated the inflammation induced by β-amyloid peptide 1-40. Furthermore, ginsennoside Rd played a role in the down-regulation of caspase-3 proteins and reduced the apoptosis that normally followed β-amyloid peptide 1-40 injection. The results of this study showed that the pretreatment of ginsennoside Rd had neuroprotective effects in β-amyloid peptide 1-40-induced AD model rat.

Ethnopharmacological Relevance: Panax ginseng, a traditional Chinese herbal medicine, has been widely used to restore the disease and enhance the healthy body in Asia for about 5000 years. The present study aimed to investigate the possible neuroprotective effects of ginsenoside Rd against OA-induced toxicity., Materials and Methods: Ginsenoside Rd was used in tauopahy models of Alzheimer's disease (AD). To mimic the in vivo or in vitro tau hyperphosphorylation, okadaic acid (OA), a protein phosphatase inhibitor, was bilaterally micro-infused into the cerebral ventricle of adult male Sprague-Dawley (SD) rats, or added in media of cultured cortical neurons. The phosphorylation levels of tau and the activities of protein phosphatase 2A (PP-2A) were measured and compared with ginsenoside Rd pretreated groups., Results: Pretreatment with ginsenoside Rd in SD rats (10mg/kg for 7 days) or in cultured cortical neurons (2.5 or 5μmol/L for 12h) reduced OA-induced neurotoxicity and tau hyperphosphorylation by enhancing the activities of PP-2A., Conclusions: The result of the present work implied that ginsenoside Rd protected SD rats and cultured cortical neurons against OA-induced toxicity. The possible neuroprotective mechanism may be that ginsenoside Rd decreases OA-induced the hyperphosphorylation of tau by the increase in activities of PP-2A. Thus, this study promises that ginsenoside Rd might be a potential preventive drug candidate for AD and other tau pathology-related neuronal degenerative diseases., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)