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Single-Cell Functional Proteome Profiling Uncovers Novel Targets for Alzheimer’s Disease

A new cyclic microchip assay analyzes hundreds of proteins in individual neurons to identify new drug targets for Alzheimer’s disease in mice and increases throughput and sensitivity of single-cell protein detection using affinity reagents. The assay achieves high throughput by repeated labeling of cellular proteins with affinity reagents and decoding biotin labelled unique DNA tags. Individual cells in a microchip well are stained for four rounds by a cocktail of DNA barcoded antibodies.

Brain Age Gap is a Composite Biomarker for Dementia Pathology or...

Brain age gap from MRI (magnetic resonance imaging) or FDG (fluorodeoxyglucose positron emission tomography) data is increased in multiple types of dementia, compared to cognitively unimpaired individuals. Therefore, investigators at Mayo Clinic conclude it may be a useful composite biomarker to identify increased risk for pathology or as a marker of disease severity in dementia. The study showed the deep learning model generates accurate age prediction for cognitively normal subjects, with a slightly better performance using an FDG PET input than MRI.

Alzheimer’s and Other Tauopathies May Depend on RNA Surveillance

Tau-induced increase in RNA export leads to a deficit in nonsense-mediated mRNA decay (NMD), a new study on fruit flies finds. Tau-induced deficits in RNA quality control are a druggable driver of neurodegeneration, the authors claim, that occurs early in the disease process and connects nuclear envelope invagination and RNA to neurodegeneration in a fly model of tauopathy. The study offers mechanistic insight into how aberrant export of RNA from the nucleus and subsequent accumulation of RNA within nuclear invaginations drive neurodegeneration in Alzheimer's disease and related tauopathies.

Neuronal Code for How Humans Negotiate Their Environment Identified

Scientists at Columbia University and the University of California, Los Angeles are the first to demonstrate that phase precession, a time coding neuronal mechanism, plays a significant role in the human brain, and links not only sequential positions, as seen in earlier animal studies, but also abstract progression towards specific goals.

Study Identifies Vulnerable Neurons in Alzheimer’s Disease

Scientists characterize selectively vulnerable neuronal populations using single-nucleus RNA sequencing in postmortem brains spanning the progression of Alzheimer’s tau neurofibrillary pathology and identify RORB as a marker of selectively vulnerable excitatory neurons and decreased homeostatic gene expression in an astrocyte subpopulation.