ABSTRACT
24 Figure 1Insomnia disorder categories: good sleeper (did not score for insomnia disorder);resolved insomnia (scored for insomnia disorder in pre-confinement);confinement insomnia (scored for insomnia disorder in confinement);and persistent insomnia (scored for insomnia disorder in pre and during confinement)[Figure omitted. See PDF]Abstract 24 Table 1Descriptives on demographic, insomnia, and sleep factors (N=74)
ABSTRACT
Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer's disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer's disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer's disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer's disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer's disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells. Collectively, our data support a link between genetic risk for Alzheimer's disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer's disease and COVID-19, and development of biomarkers to track disease progression.
Subject(s)
2',5'-Oligoadenylate Synthetase/genetics , Alzheimer Disease/genetics , COVID-19/genetics , Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Patient Acuity , Adolescent , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Cells, Cultured , Female , Gene Regulatory Networks/genetics , Genetic Predisposition to Disease/epidemiology , Humans , Induced Pluripotent Stem Cells/physiology , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Young AdultABSTRACT
The purpose of this article is to outline the convergence - an intellectual as well as a political convergence - of two concepts that will play a critically important role in fashioning a more inclusive and more sustainable model of development in the post-Covid world. The first concerns the concept of the Foundational Economy, which offers a new lens through which to view and value social and economic activity by highlighting the significance of a range of goods and services that loom large in terms of meeting human needs. The second concerns the concept of Experimental Governance, which offers a multilevel framework in which to understand place-based social innovation, a framework which overcomes the shortcomings of principal-agent models of collective action as well as the binaries associated with top-down versus bottom-up theories of change.
ABSTRACT
During the Covid-19 global pandemic, and in the face of an imminent crisis derived from it, various concerns arise regarding the economic consequences that the situation will bring, as well as whether the response of the different governments will be enough in the long term. The Foundational Economy Collective proposes, for the European context in particular, a series of points and lessons for the economic policy decisions that emerge from this crisis in order to stimulate national and regional economies once the pandemic is over.