44 research outputs found

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

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    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

    Fruit-bearing branchlets are carbon autonomous in mature broad-leaved temperate forest trees

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    In order to evaluate the degree of carbon autonomy for fruit development, the carbon source-sink relationship in fruit-bearing branchlets of mature deciduous forest trees was manipulated in situ. The tests included half and complete defoliation, girdling or the combination of both treatments, which were applied on fruiting branchlets by using a canopy crane. Concentrations of non-structural carbohydrates (NSC) were analysed in different branchlet tissues and fruits, to identify situations of carbon imbalances induced by the treatments. NSC concentrations of branchlets were generally lower under treatments resulting in decreased fruit growth. All three investigated species (Carpinus betulus, Fagus sylvatica and Tilia platyphyllos) exhibited complete carbon autonomy of fruiting at the level of whole, undisturbed branchlets, since neither a decrease of total infructescence biomass, nor of individual fruit mass occurred on girdled, un-defoliated branchlets. On girdled, 100% defoliated branchlets, fruit biomass relative to controls decreased by approximately 50% in Carpinus and Tilia, but by almost 80% in Fagus, which can be explained by different proportions of photosynthetically active infructescence tissues among the species. In contrast to the other two species, Tilia branchlets did not import carbon to compensate for assimilate loss after defoliation
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