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

Chromosome comparison between two species of Phyllostomus (Chiroptera - Phyllostomidae) from Eastern Amazonia, with some phylogenetic insights

The karyotypes of Phyllostomus discolor and P. hastatus from Eastern Amazonia were studied by G-, C-, G/C sequential and Ag-NOR techniques. Both species presented 2n = 32, with the autosome complement composed of 30 bi-armed in P. discolor and 28 bi-armed plus 1 acrocentric in P. hastatus. In both species, the X chromosome is medium submetacentric while the Y is minute acrocentric. The present study found only one difference between the karyotypes of P. discolor and P. hastatus: the smallest autosome (pair 15) is bi-armed in discolor and acrocentric in hastatus, a result best explained by pericentric inversion. The C-banding revealed constitutive heterochromatin only at the centromeric regions of all chromosomes, with the NOR site located at the distal region of short arm of pair 15, in both species. The taxon P. discolor is considered primitive for genus Phyllostomus and the bi-armed form of pair 15 is the assumed primitive condition which, rearranged by a pericentric inversion originated the acrocentric from found in P. hastatus.<br>Os cariótipos de Phyllostomus discolor e P. hastatus da Amazônia oriental são estudados por bandeamentos G, C, G/C sequencial e coloração Ag-NOR. Ambas as espécies apresentaram 2n = 32, sendo o complemento autossômico composto por 15 pares bi-armed em P. discolor e 14 bi-armed mais 1 par acrocêntrico em P. hastatus. O cromossomo X é um submetacêntrico médio e o Y é um pequeno acrocêntrico em ambas as espécies. O presente estudo encontrou apenas uma diferença entre os cariótipos de P. discolor e P. hastatus: o menor autossomo (par 15) é metacêntrico em discolor e acrocêntrico em hastatus. Este resultado é melhor explicado por uma inversão pericêntrica. O bandeamento C revelou heterocromatina constitutiva na região centromérica de todos os cromossomos, e os sítios NOR foram localizados na região distal do par 15, em ambas as espécies. O táxon P. discolor é considerado primitivo para o gênero Phyllostomus e supõe-se que a forma metacêntrica do par 15 seja a condição primitiva, que foi rearranjada por uma inversão pericêntrica, originando a forma acrocêntrica encontrada em P. hastatus

Laser-based systems for trace gas detection in life sciences

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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. © 2022, The Author(s)