Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD

The sheep performances in a grassland-based system is improved when combined with beef cattle

The specifications and the high price of feed in organic farming require implementing forage fattening. Based on the principles of agroecology, we hypothesized that the livestock farming system performance (animal productivity, environment and level of inputs) would be improved by associating beef cattle and sheep, allowing better valorisation of forages and parasitism control for the sheep. Three suckler farming systems (cattle (CAT), sheep (SH), mixed sheep-cattle (MIX)) were managed for 5 years into separate farmlets in INRAE Herbipole experimental farm, in order to test this hypothesis and the feasibility of producing beef and sheep-meat with only grass in a context of permanent grassland at 1000-1,300 m asl. The results showed that MIX sheep took advantage of the association, with a lower use of concentrates and anthelmintics and a better lamb growth rate compared to SH. Despite a satisfactory degree of fatness, the carcass of young cattle were considered too light by the industry with poor price. The high need for conserved forages for beef fattening in winter, coupled with droughts, has generated additional costs through the purchase of hay

Productivity and technical efficiency of suckler beef production systems: trends for the period 1990 to 2012

International audienc

A2A adenosine receptor deletion is protective in a mouse model of Tauopathy

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe