Search

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.

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

Electrons in uranium-based materials are often on the border between localised and itinerant behaviour, which can lead to unusual magnetic behaviour. Here the authors combine experiment and theory to show that USb₂ may be an unusually high temperature example of a singlet-ground-state magnet.

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.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

RhoA, a ubiquitous intracellular GTPase, mediates cytoskeletal responses to extracellular signals. A 2.1 Å resolution crystal structure of the human RhoA–GDP complex shows unique stereochemistry in the switch I region, which results in a novel mode of Mg2+ binding.

Sodium ion batteries offer more cost-effective storage than lithium and could be used for grid-scale energy storage. Here, the authors demonstrate a full cell based on a MnHCMn anode and an organic-aqueous cosolvent electrolyte. X-ray spectroscopy evidence further suggests the presence of Mn(I).

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.

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.

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.

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.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The surface electrons in a topological insulator are resistant to localization by nonmagnetic disorder, but are affected by lattice disorder. Here, the authors show that resonance states near lattice defects on the surface have significance beyond the localized regime usually associated with impurity bands.

In vivo screening of pro-metastatic factors in a genetically engineered mouse model of lung cancer uncovered the CD109–JAK–STAT3 axis as a key contributor of metastatic dissemination of lung cancer cells. Activation of this pathway predicts poor outcome in patients with cancer, and its pharmacological inhibition dramatically reduces the metastatic ability of tumor cells, suggesting that it might be an effective intervention in patients.

Yoon Shin Cho, Mark Seielstad and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes in individuals of east Asian ancestry. They identify eight new loci associated with type 2 diabetes.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Welm and colleagues present a biobank of human-derived xenografts and organoids and demonstrate its value for high-throughput drug screening and applied precision medicine.

The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

This Perspective lays out the impetus and goals of the Cellular Senescence Network established to comprehensively identify and characterize senescent cells (SnCs) across tissues and lifespan, providing a publicly available SnC atlas.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

Molecular and structural characterization is reported for a new broad and potent monoclonal antibody against HIV that binds to an epitope bridging the gp41 and gp120 subunits — the antibody affects a step in virus entry after binding to CD4 and before engagement of CCR5.

A yeast surface display screen identifies five Aedes aegypti salivary proteins that are antigenic in mice repeatedly bitten by these mosquitoes. Antiserum against one of these proteins, Anopheles gambiae bacteria-responsive 1, partially protected mice against lethal mosquito-borne Zika virus infection.

Martensite in Ti-6Al-4V is known to decompose under heating. This study employs rapid laser heating in situ in a synchrotron to study changes in the diffraction profiles during the martensite decomposition process.

GNPS is an open-access community-curated analysis platform for sharing natural product mass spectrometry data that enables continuous, automatic reanalysis of deposited 'living' data sets.

SenNet Consortium members review current and emerging methodologies for spatially resolved mapping of senescent cells. They discuss their limitations and challenges involved in the aim of creating a comprehensive atlas of senescent cells during aging.