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

Resposta de cultivares de trigo à infestação do pulgão Rhopalosiphum padi Wheat cultivars response to Rhopalosiphum padi infestation

O objetivo deste trabalho foi avaliar a resposta de oito cultivares comerciais de trigo (BRS 194, BRS 208, BRS Camboatá, BRS Guabiju, BRS Guamirim, BRS Louro, BRS Timbaúva e BRS Umbu) à infestação do pulgão Rhopalosiphum padi (Hemiptera: Aphididae). O experimento foi realizado na Embrapa Trigo, em telado, em blocos ao acaso, com oito tratamentos e seis repetições, dispostos em parcelas subdivididas. As parcelas principais receberam os tratamentos com e sem infestação de pulgões, e as subparcelas foram compostas pelas cultivares. A infestação com os pulgões (20 adultos ápteros por planta) foi realizada aos 12 dias após a emergência das plantas, quando se encontravam no início do afilhamento, e foi mantida durante 15 dias. As cultivares avaliadas responderam diferentemente à infestação do pulgão R. padi. A cultivar BRS Timbaúva é a mais resistente, e as cultivares BRS Umbu e BRS Guabiju são as mais suscetíveis ao pulgão, quanto ao crescimento e a capacidade produtiva de plantas.<br>The objective of this work was to evaluate the response of eight commercial wheat cultivars (BRS 194, BRS 208, BRS Camboatá, BRS Guabiju, BRS Guamirim, BRS Louro, BRS Timbaúva e BRS Umbu) to the infestation of Rhopalosiphum padi (Hemiptera: Aphididae). The experiment was carried out at Embrapa Trigo, in greenhouse conditions. It was used the randomized block design, in a split-plot array, with eight treatments and six replicates. The plots received treatments with or without infestation with aphids, and the split-plots were composed by the cultivars. The infestation with aphids (20 wingless adults per plant) was done 12 days after plant emergency, in the beginning of tillering, and was kept for 15 days. The cultivars responded differently to the infestation with aphids. BRS Timbaúva cultivar is more resistant, and BRS Umbu and BRS Guabiju cultivars are more susceptible to R. padi, concerning plant growth and plant yield