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

Macrófitas aquáticas de ilhas flutuantes (baceiros) nas sub-regiões do Abobral e Miranda, Pantanal, MS, Brasil Aquatic macrophytes of floating mats (" baceiros" ) in the Abobral and Miranda Pantanal Wetlands, Mato Grosso do Sul State, Brazil

A associação entre as formas biológicas flutuante e epífita, relacionadas a macrófitas aquáticas, constitui o que se chama genericamente de ilha flutuante. Esta denominação é aplicada ao estabelecimento de uma ou mais epífitas sobre indivíduos vivos de espécies flutuantes, como sinônimo de camalotal ou, ainda, para se referir à vegetação flutuante que se desenvolve sobre um solo orgânico em decomposição (histossolo). Realizou-se o levantamento das espécies presentes em cinco baceiros nas sub-regiões pantaneiras do Abobral e Miranda e o estabelecimento das similaridades florísticas entre estes, a fim de evidenciar aspectos da dinâmica sucessional de ilhas flutuantes. Foram encontradas 66 espécies de macrófitas aquáticas epífitas, distribuídas em 27 famílias, sendo Cyperaceae e Poaceae as mais representativas. O número de espécies por baceiro variou de 7 a 39, sendo os táxons comuns a todos esses Ludwigia leptocarpa (Nutt.) H. Hara e Oxycaryum cubense (Poepp. & Kunth) Palla, ao nível específico, e Asteraceae, Cyperaceae, Onagraceae, Poaceae e Polygonaceae, com relação às famílias. Outras formas biológicas, além da epífita, foram encontradas associadas aos baceiros, ou ainda, se mostraram adaptadas às condições do histossolo, podendo ser consideradas " epífitas casuais" . Baceiros em estágios sucessionais mais próximos apresentam maior similaridade florística e, no geral, quanto mais avançada a sucessão natural, maior a riqueza específica.<br>The association between floating and epiphytic biological forms, regarding aquatic macrophytes, creates what are called floating mats. This concept refers to the establishment of one or more epiphytes on live individuals of floating species, as a synonym of " camalotal," or applied to floating vegetation that grows on organic soil in decomposition (histosol). A checklist of species was made of five floating mats in the Abobral and Miranda Pantanal Wetlands and floristic similarities among these mats were calculated to show aspects of sucessional dynamics on floating mats. A total of 66 species of epiphytic aquatic macrophytes were found, distributed in 27 families, Cyperaceae and Poaceae being the most representative. The number of species per mat varied from 7 and 39, with some taxa common to all mats, such as Ludwigia leptocarpa (Nutt.) H. Hara and Oxycaryum cubense (Poepp. & Kunth) Palla, at the specific level, and Asteraceae, Cyperaceae, Onagraceae, Poaceae and Polygonaceae, at the family level. Other biological forms besides epiphytes were found associated with " baceiros" or adapted to histosol conditions, being considered " casual epiphytes" . " Baceiros" in similar successional stages of development have high floristic similarity, and in general, the more advanced the natural succession, the higher the number of species

Reducing the incidence of twins and triplets

Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease