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Measurements of dopamine, serotonin and norepinephrine in the caudate of conscious humans reveal a neurochemical boundary between patients with essential tremor and Parkinson’s disease based on serotonin release evoked by monetary offers.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Using three-dimensional correlative light and electron microscopy of Lewy bodies and Lewy neurites in postmortem brains of Parkinson’s disease patients, researchers show that the major constituents are membranes rather than proteinaceous filaments.

White adipose tissue (WAT) dysfunction leads to ageing-related metabolic disorders. Here, the authors show that the FMO3-TMAO axis in adipocytes induces senescence and inflammation in WAT microenvironment via NLRP3 inflammasome, leading to systemic glucose, lipid, and energy dysregulation in ageing

In this article, Batten and colleagues measure fast neurotransmitter release in patients undergoing awake brain surgery. As volunteers play an economic game with human and computer partners, dopamine and serotonin track social context and value statistics.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

A machine learning approach is presented to identify dominant patterns in disease progression in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The nonlinearity of ALS progression has important clinical implications.

Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphorylating Drp1 in the cytoplasm and show overexpression suppresses a Parkinson’s disease model.

Two BCMA-targeted CAR T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have been approved for the treatment of multiple myeloma (MM). Here the authors report distinct expansion, phenotype, function, and toxicity of cilta-cel vs. ide-cel CAR T cells in a realworld cohort of patients with MM.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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 genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Chiou et al. provide a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques.

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.

Evan Eichler and colleagues explore the structural diversity and ancestral origins of the 17q21.31 inversion region. They find that complex duplication architectures have arisen independently on both inversion haplotypes and have recently reached high frequencies among Europeans, either through extraordinary genetic drift or selective sweeps.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Parkinson’s diseases and other synucleinopathies are on the verge of a major paradigm shift toward being defined and staged by their biology, rather than symptoms; this Perspective offers context on progress, needs and opportunities toward this goal.

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.

Genetic studies in Africa can provide a unique window into hereditary neurological diseases (HNDs). This Review highlights the benefits and challenges of conducting genetic research in Africa and summarizes the insights into HNDs gained from previous studies on the continent.

Epigenetic clocks based on DNA methylation levels are estimators of chronological age. Here, the authors perform a GWAS of epigenetic aging rates in blood and find SNP variants in the TERT locus associated with increased intrinsic epigenetic age are also associated with longer telomeres.

It is unclear how bacterial chemoreceptors are reliably targeted to the cell poles. Here, Draper and Liphardt show that chemoreceptor localization is highly sensitive to membrane curvature in live bacteria, and engineer curvature sensitivity into several multi-component synthetic protein complexes.

The mechanisms of pathological astrocyte responses during multiple sclerosis remain unclear. Kadowaki et al. found in MS mouse models that CLEC16A suppresses astrocyte pathogenic activities related to mitochondria by boosting mitophagy.

Drp1 is the master regulator of mitochondrial fission, which has important impact on cellular functions. Here, Yang et al identified evolutionarily conserved proteins Clueless and its homolog CLUH as key regulators of Drp1 that function via translation of Drp1 receptors MiD49 and Mff.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Development of a constraint model specifically for mitochondrial DNA and applied to data from the Genome Aggregation Database provides insights into which sites in the mitochondrial genome are important for health and disease.

It has long been thought that motor control is achieved through the balanced activity of two distinct pathways through the basal ganglia that have opposing effects, but this has never been functionally verified. These authors directly test this hypothesis with optogenetic activation of different populations of mouse striatal neurons, and not only trace functional connectivity but demonstrate opposing effects on motor behaviour in a parkinsonian model.

Cryo-electron microscopy structure of the human dopamine transporter in complex with multiple inhibitors illuminates mechanisms of allosteric inhibition.