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Genome-wide association studies (GWAS) of deep learning-derived measurements of aortic valve function, along with multitrait analyses incorporating disease-based GWAS, identify 166 genetic loci associated with aortic valve function or aortic stenosis.

Across 13 longitudinal studies (3,737 adults), the authors show that brain atrophy parallels memory loss, with a stronger coupling in later life. APOE ε4 increases decline, yet genetic risk does not modify the brain–memory relationship.

In this Review, Nicholas Chew and colleagues use epidemiological data on the cardiovascular–liver–metabolic disease syndemic to illustrate current and future projections on the burden of these diseases and their risk factors, and propose a unified framework for integrating and implementing effective multisystem interventions to tackle key components of this syndemic.

This study reports clusters of ipsilateral eye preferring neurons in layer 4 of mouse visual cortex, extending into layer 2/3 and upper layer 5. This column-like pattern for ocular dominance expands our understanding of the functional organization in neocortex.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

The role of olfactory pathways in the development of neurodegeneration in Alzheimer’s disease is not well understood. Here, the authors show odor identification deficits are predictive of tau accumulation and progression in olfactory pathways, and that tau spreads from medial temporal lobe structures towards the olfactory system.

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.

Neural mechanisms underlying representational drift are not fully understood. Here authors report that the preferred orientation of mouse visual cortex neurons drifts over time. Altering visual experience does not change drift magnitude, but rather its direction, such that neurons’ tuning matches the statistics of the environment.

Antiretroviral therapy alone is insufficient in curing HIV-1 infection, due to latent viral reservoir persistency. Here, authors explore the post-virologic control of combining active and passive immunisation with vesatolimod, in a SHIV-infected rhesus macaque model.

The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.

Multiple myeloma (MM) is treated with induction chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. Here, the authors show that the presence of clonal haematopoiesis of indeterminate potential (CHIP) at time of ASCT is associated with adverse outcomes in MM patients.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

An in vitro human tonsil tissue-based system captures key features of a functional germinal center and can be used to study humoral immune responses to vaccines, new antigens and adjuvants.

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.

Memory lapses can occur due to ineffective encoding, but it is unclear if targeted brain stimulation can improve memory performance. Here, authors use a closed-loop system to decode and stimulate periods of ineffective encoding, showing that stimulation of lateral temporal cortex can enhance memory.

Dendritic spine morphogenesis is sensitive to experience-dependent plasticity, but whether or not experience-induced structural changes outlast the experience itself is unknown. This paper reveals that long-lived spine density increases in response to monocular deprivation that persist beyond the duration of time the eye was closed. Subsequent deprivation fails to induce further spine density increases, suggesting initial experience may provide a structural experience 'trace' that could be utilized in response to further functional shifts.

Goltstein et al. investigate the role of mouse visual cortical areas in information-integration category learning. They report widespread changes in neuronal response properties, most prominently in a higher visual area, the postrhinal cortex.

Diabetic ketoacidosis (DKA) is the leading cause of death, morbidity and excessive health-care utilization and costs in patients with type 1 diabetes mellitus; DKA is common at initial diagnosis, but uncommon thereafter. A new study has determined the risk factors for multiple DKA episodes and their relationship to the risk of death.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the 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.

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.