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Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Preclinical research indicates that various drugs approved for indications such as hypertension and diabetes could also have potentially beneficial effects in Alzheimer's disease, and for some drugs the evidence is also supported by epidemiological data or preliminary clinical trials. This article presents a formal consensus evaluation of these drug repositioning opportunities, and highlights several compounds for which sufficient evidence is available to encourage further investigation and potential progression to clinical trials in Alzheimer's disease.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Here, Dzanibe et al show that in utero HIV/ARV exposure sequentially disrupts infant immunologic trajectories, beginning with NK cells that predict vaccine antibody responses and followed by delayed T cell memory maturation linked to skewed TCR clonality.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

The immune-system–brain interface is a crucial route for communication between the brain in health and disease and environmental pathogens and toxins. Can systemic infections and inflammation associated with chronic neurodegenerative diseases exacerbate symptoms and drive the progression of neurodegeneration?

Muscles contain interdigitating filaments of actin and myosin, which are connected by cross-bridges (myosin heads) driven by ATP hydrolysis. What goes on in molecular terms during muscle contraction remains a matter of debate, however, and was the topic of a European meeting in September. Discussion centred on crystal structures of the cross-bridge and actin at atomic resolution, and the development of assays to follow events at the single-molecule level. Fresh ways of looking at muscle disease also came in for consideration.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Multistage gene burden analysis in exome sequencing data from 32,558 individuals identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease.

Acne vulgarisis a common, inflammatory skin disorder. Here the authors carry out a genome-wide association study and identify three genetic variants that associate with an increased risk of developing acne, which together suggest a mechanistic role for the TGFβ cell signalling pathway in acne development and progression.

As a response to accumulation of debris and abnormally folded proteins during neurodegeneration, microglia multiply and adopt a chronically activated state. This process, referred to as priming, makes microglia susceptible to a secondary inflammatory stimulus, often arising from a systemic disorder with an inflammatory component, such as diabetes. Primed microglia react to the secondary inflammatory stimulus with an exaggarated response, which can further exacerbate neurodegeneration.

Microglia rapidly adopt an activated phenotype in response to brain injury and disease, which suggests that they could act as diagnostic markers of neurodegenerative disease onset or progression. In this article, Perry et al. review the relationship between activated microglia and neurodegenerative diseases and discuss the interactions between microglial phenotype, systemic inflammation and neurodegenerative disease progression.

Acne vulgaris is a chronic inflammation of the skin, the genetic basis of which is incompletely understood. Here, Petridis et al. perform GWAS and meta-analysis for acne in 26,722 individuals and identify 12 novel risk loci that implicate structure and maintenance of the skin in severe acne risk.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

Julie Williams, Michael Owen and colleagues report staged follow-up and meta-analyses of genome-wide association studies for Alzheimer's disease from the GERAD+ consortium. They identify common variants at ABCA7 and MS4A6A/MS4A4E associated with Alzheimer's disease and support for several additional susceptibility loci.

Philippe Amouyel, Julie Williams, Gerard Schellenberg, Sudha Seshadri and colleagues report a meta-analysis of genome-wide association studies for late-onset Alzheimer's disease in 17,008 cases and 37,154 controls with replication in an additional 8,572 cases and 11,312 controls. They identify 11 loci newly associated with Alzheimer's disease.

Julie Williams and colleagues report a genome-wide association study for Alzheimer's disease. They identify variants at the CLU and PICALM loci associated with susceptibility to late-onset Alzheimer's disease.

Whole-exome sequencing reveals that a rare variant of phospholipase D3 (PLD3(V232M)) segregates with Alzheimer’s disease status in two independent families and doubles risk for the disease in case–control series, and that several other PLD3 variants increase risk for Alzheimer’s disease in African Americans and people of European descent.