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Impaired Aβ clearance in late-onset Alzheimer’s disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry Aβ in peripheral circulation and CSF in AD, suggesting a role in Aβ clearance.

Ossenkoppele, Salvado et al. show that plasma p-tau217 and tau-PET predict cognitive decline equally well among cognitively unimpaired individuals. Their combined use further boosts prognostic accuracy. A sequential approach can enhance precision and efficiency of preclinical Alzheimer trials.

Accumulating evidence from several studies points to the normal function of presenilin 1 and suggests how the mutant protein contributes to deposition of amyloid plaques in Alzheimer's disease (pages 756–760).

Cardiovascular and metabolic risk factors (CVM) impact brain structure and increase dementia risk. Here, the authors developed and validated machine learning models to measure the neuroanatomical changes in people with cardiovascular and metabolic diseases that are cognitively unimpaired.

DOPA decarboxylase (DDC) in cerebrospinal fluid has great diagnostic potential for Lewy body disorders. Here, the authors report limited diagnostic potential of plasma DDC and a strong association with dopaminergic treatment.

Assessing brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies, a generative model identifies five dominant patterns of brain atrophy, with specific associations with biomedical, lifestyle and genetic factors.

Abnormal amyloid and tau PET in cognitively unimpaired individuals is strongly associated with short-term cognitive decline and subsequent development of dementia.

Many diseases can display distinct brain imaging phenotypes across individuals, potentially reflecting disease subtypes. However, biological interpretability is limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Here, the authors describe a deep-learning method that links imaging phenotypes with genetic factors, thereby conferring genetic correlations to the disease subtypes.

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

Site-specific hyperphosphorylations of tau in the cerebrospinal fluid change with disease course, and correlate with pathology and cognitive decline in dominantly inherited Alzheimer’s disease.

The fabrication of vascularized 3D tissues requires an understanding of how material properties govern endothelial cell invasion into the surrounding matrix. Here the authors integrate a non-swelling synthetic hydrogel with a microfluidic device to study chemokine gradient-driven angiogenic sprouting and find that matrix degradability modulates the collectivity of cell migration.

Millions of primary IgG-secreting cells from mouse and human are characterized for activity and antibody sequence at the single-cell level.

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.

The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.

Results from the phase 2/3 clinical trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease reveal no beneficial effects on cognitive measures despite a significant reduction in amyloid plaques and other key biomarkers in those treated with gantenerumab.

Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.

Different types of atrophy in Alzheimer’s disease may reflect different disease stages or biologically distinct subtypes. Here the authors use longitudinal neuroimaging data to demonstrate five distinct patterns of atrophy with different demographical and cognitive characteristics.

The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

This study supports neurofilament light chain protein (NfL) in both cerebrospinal fluid (CSF) and blood as an early marker of neurodegeneration in Alzheimer’s disease but suggests that NfL in CSF may be better suited than blood for monitoring clinical trial outcomes in symptomatic patients.

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.

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.

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

This study shows that among healthy adults tracked across their lives, brain atrophy rates correlate with genetic risk for Alzheimer’s and memory decline, and that degeneration in Alzheimer’s-vulnerable brain regions is a continuous phenomenon.

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.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

In a longitudinal cohort of familial Alzheimer’s disease patients, the rate of change of blood biomarker levels identifies disease carriers much earlier than absolute levels and predicts both neurodegeneration and cognitive decline.

The knowledge of imaging and fluid biomarkers gained from longitudinal observational studies of Alzheimer disease has recently been translated to a cross-sectional study of randomly selected, cognitively unimpaired elderly individuals. This is the first time that a two-feature biomarker classification system has been applied to a population-based cohort.

Cortical thickness is asymmetric, and cortical thinning occurs with age and in disease. Here the authors investigate if both cortices thin at the same rate or if the thicker hemisphere declines faster in aging and in Alzheimer’s disease.

The Dominantly Inherited Alzheimer Network neuroimaging repository is a free resource consisting of PET and MRI scans from 533 individuals across 206 families who are deeply phenotyped with genetic, clinical, cognitive and biofluid sampling.

The authors present a high-throughput single-cell ChIP-seq method with coverage of up to 10,000 loci per cell. They identify diverse chromatin landscapes in breast cancer cells characterized by dynamic H3K27me3 levels.