New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Participative backcasting: A tool for involving stakeholders in local sustainability planning

This paper reports on the use of a backcasting approach with local stakeholders in five European cities where several Images of the Future were formulated for household consumption in sustainable cities. The aim was to find methods for inspiring local stakeholders to participate in discussions about sustainability with a long-term perspective. Previous exercises of similar kinds have mainly involved experts. A method based on workshops and back-office work was developed and is described and analysed here, together with the results obtained. The outcomes in terms of ideas, votes and dimensions are also discussed. The findings suggest that the method worked reasonably well, with the process quality receiving the highest ratings. The quality of outcomes was perceived as less reliable. Adaptations should include more efforts to recruit participants with varied backgrounds and more innovative approaches for liberating subjects' minds during the time travel stage of the process. The outcomes obtained show that there appears to be a common set of popular ideas for more sustainable everyday city life in the EU, including more local and organic food, a greener environment, better public transport and opportunities for non-motorised transport and reorientation of values. (c) 2007 Elsevier Ltd. All rights reserved