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This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

The National Institute of Allergy and Infectious Diseases (NIAID) hosted a two-day virtual workshop on leveraging microbial exposure to improve mouse models of human immune status and disease. The workshop’s objective was to evaluate the current state of knowledge in the field and to identify gaps, challenges and future directions.

Phylogenetic diversity is decoupled from taxon diversity for the Cape Floristic Region of South Africa, a biodiversity hotspot. It turns out that the more species-rich western part of the Cape has lower evolutionary potential than the more neglected eastern part, with important consequences for conservation planning.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

As metabolic reactions are often in equilibrium, product sequestration is often used to drive engineered pathways forward. For n-butanol, however, this is not possible; instead, introducing kinetic barriers for backwards reactions significantly increases product yield.

Nitric oxide deficiency promotes tuberculosis through increased neutrophilic inflammation.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

Analysis of bronchoalveolar lavage fluid samples from patients with SARS-CoV-2-induced respiratory failure suggests that SARS-CoV-2 infects alveolar macrophages to cause release of T cell chemoattractants, thereby inducing local inflammatory cytokine release and further T cell activation, ultimately resulting in a positive feedback loop that drives alveolar inflammation.

David Whitcomb, Bernie Devlin and colleagues report the results of a genome-wide association study of pancreatitis. They identify common variants at two loci associated with risk of this disease, including one on the X chromosome that shows strong evidence of interaction with alcohol consumption.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Lethal pediatric tumors bearing a particular histone H3 mutation upregulate the disialoganglioside GD2, thereby making these tumors susceptible to chimeric antigen receptor T cell–based immunotherapy.

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.

scHLApers is an analysis pipeline that quantifies single-cell expression of HLA genes using a personalized genomic reference. Mapping of HLA expression quantitative trait loci at single-cell resolution identifies dynamic effects across cell states.

Alison Klein and colleagues report a genome-wide meta-analysis to identify loci associated with pancreatic cancer risk. They identify associated variants at 17q25.1, 3q29, 7p13 and 2p13.3.

The evolution of stent design has reduced the incidence of stent thrombosis, meaning that the duration of dual antiplatelet therapy after percutaneous coronary intervention (PCI) might be shortened. In this Review, the authors describe the current evidence base and ongoing clinical trials into the use of P2Y₁₂ inhibitor monotherapy after PCI.

In this Review, the authors propose that disease-associated genetic variants modulate signalling downstream of B cell receptors, Toll-like receptors and cytokine receptors in B cells to drive autoimmune responses. This altered signalling favours a naive B cell repertoire that is skewed towards self-reactivity and promotes the peripheral activation of autoreactive B cell clones.