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

Lixiviação de nitrogênio em latossolo incubado com lodo de esgoto Nitrogen leaching in a latosol incubated with sewage sludges

Lodo de esgoto contém teores elevados de N orgânico. Se for aplicado em quantidade excessiva em solos, há risco de poluição de águas subsuperficiais com nitrato, produto da mineralização do N. Por essa razão, um dos critérios agronômicos para a determinação da taxa máxima de aplicação do lodo de esgoto é a quantidade de N mineral que será disponibilizada às culturas. Neste trabalho, são apresentados os resultados relativos à lixiviação de N mineralizado em um Latossolo Vermelho distroférrico incubado durante 224 dias com dois tipos de lodo de esgoto anaeróbios, um de origem urbana (Franca, SP) e outro com presença de despejos industriais (Barueri, SP). Cada lodo de esgoto foi aplicado em quatro doses, contendo 0,13, 0,3, 0,5 e 1,0 g kg-1 de N orgânico. Essa quantidade de substrato mineralizável foi equivalente a 5, 11, 22 e 43 t ha-1 de lodo de Franca, e a 8, 15, 31 e 61 t ha-1 de lodo de Barueri. O experimento foi conduzido em colunas de percolação, sob temperatura de 25 a 28 °C em laboratório, fazendo-se lixiviações com solução extratora de KCl 0,01 mol L-1. Foram determinadas as quantidades de N mineral (N-NH4+ e N-NO3- + N-NO2-) extraídas nos percolados em doze épocas. Houve correlação significativa entre as quantidades aplicadas de N na forma orgânica e as quantidades de N mineralizadas durante a incubação nos dois tipos de lodo avaliados. O potencial de mineralização estimado pelo modelo exponencial simples foi de 73 mg kg-1 de N no solo sem aplicação de lodo, e aumentou de 107 para 224 mg kg-1 e de 132 para 364 mg kg-1 nos tratamentos com o lodo de esgoto de Franca e de Barueri, respectivamente. A fração de mineralização potencial do N orgânico dos dois tipos de lodo de esgoto decresceu com o aumento das doses aplicadas: 26, 25, 21 e 14 % para o de Franca, e 43, 39, 34 e 27 % para o de Barueri. Em consequência, o potencial de lixiviação de N no Latossolo aumentou de 46 para 207 % com as doses do lodo de Franca, e de 81 para 399 % com as doses do lodo de Barueri.<br>Sewage sludges contain high levels of organic N. If these residues are applied in excess to soils, there is the risk of polluting the groundwater with nitrate, a product of N mineralization. For this reason, one of the criteria underlying the determination of the maximum N application rate to soils is the crop available N. This paper presents the results of a 224 day laboratory leaching study on organic N mineralization of anaerobically-digested sewage sludges from two treatment plants, namely Franca (urban sludge) and Barueri (urban-industrial sludge), both located in São Paulo State, Brazil. The sewage sludges were applied to 0-0.20 m Latosol (Oxisol) samples at four rates, containing 0.13, 0.3, 0.5 and 1.0 g kg-1 of organic N; these treatments were equivalent to the soil application of 5, 11, 22 and 43 t ha-1 of Franca sewage sludge and to 8, 15, 31 and 61 t ha-1 of Barueri sewage sludge. The soil samples with treatments were incubated in percolation tubes at temperatures between 25 and 28 °C. The tubes were periodically leached (12 times) with 0.01 mol L-1 KCl, and N-NH4+ and N-(NO3- + NO2-) were determined in the leachates. During the incubation, there was a significant correlation between the rate of organic N applied as sludges and the net inorganic N accumulation in the leachates, for both sludges. The potential N mineralization estimated by the single exponential model for the soil without sludge was 73 mg kg-1 of N, and increased from 107 to 224 mg kg-1 and from 132 to 364 mg kg-1 in the Franca and Barueri-treated soils, respectively. The potential mineralization fraction of organic N in the residues decreased with increasing rates: 26, 25, 21 and 14 % for the Franca, and 43, 39, 34 and 27 % for Barueri sewage sludge. Thus, the potential for N leaching in the studied Oxisol increased from 46 to 207 % when increasing doses of Franca sewage sludge were applied, and from 81 to 399 % under increasing doses of Barueri sludge