Alzheimer's disease research and treatments

Neuronal and glial transcriptional states vary with proximity to tangle-bearing neurons in the human entorhinal cortex

The paper examines how proximity to tangle-bearing neurons affects transcriptional states in human entorhinal cortex cells, finding that nearby neurons and glia show distinct molecular signatures related to disease.

Disrupting SORL1-retromer endosomal recycling in mice drives the age-dependent neurodegenerative signature of Alzheimer's disease

This study shows that disrupting SORL1-retromer recycling in mice leads to age-dependent brain atrophy resembling Alzheimer's disease, which can be reversed by restoring SORL1 function.

Automated multiscale high-content imaging connects plaque population heterogeneity to localized synapse loss

The paper develops an automated high-content imaging workflow to quantify synapse loss associated with amyloid beta plaques in mouse brains, finding that large cored plaques primarily drive synapse loss.

Pregnancy History and Loss of Normal PSEN2 Function Impact Female Late-Life Cognitive Processing, Inhibitory Signaling, and Gliosis

The paper investigates how pregnancy history and PSEN2 deficiency affect cognitive function and neurobiology in aged female mice, finding no synergistic effects.

Opposing Regulation of Tau Condensation by Phosphorylation Levels and Molecular Chaperone Interactions

This study investigates how phosphorylation levels and the molecular chaperone Bri2 BRICHOS opposingly regulate Tau condensation and aggregation, revealing their roles in tauopathies.

Aβ42 facilitates the activation of Discoidin Domain Receptor 2 and Its nuclear enrichment in Alzheimer's Disease Model

This study shows Aβ42 activates DDR2 in Alzheimer's disease models by non-canonically bypassing collagen ligands and promotes its nuclear enrichment, with structural insights into the mechanism and potential therapeutic inhibition.

Two polymorphs of an independent amyloid core in medin's C-terminal region.

The paper identifies two polymorphs of an independent amyloid core in the C-terminal region of medin, showing it has multiple aggregation-prone regions.

The Alzheimer's disease-associated rs28834970 variant in PTK2B impairs electrical activity and regulates Tau phosphorylation and APP processing in human neuronal cultures

This study identifies the rs28834970 variant in PTK2B as a risk factor for Alzheimer's disease, showing it impairs PYK2 function, increases Tau phosphorylation, and alters APP processing in human neuronal cultures.

4-methylumbelliferone attenuates amyloid pathology and learning deficits in the APP/PS1 mouse model

This study shows that 4-MU treatment reduces amyloid pathology and improves memory in APP/PS1 mice.

Anterior thalamic nucleus inputs to the retrosplenial cortex are unperturbed in the hAPP-J20 mouse model of Alzheimer's disease

The paper investigates whether AD-like pathology affects thalamic projections to the retrosplenial cortex in hAPP-J20 mice, finding no impairment in synaptic strength or c-Fos expression.

Tau is an m6A-associated RNA binding protein that causes RNA dysregulation in disease

The paper identifies tau as an m6A-associated RNA binding protein that causes RNA dysregulation in MAPT coding-variant patients and V337M iNeurons.

Single-Nucleus Profiling Reveals Neuronal Metabolic Collapse During the Transition to Alzheimer's Disease Dementia

This study uses single-nucleus RNA-sequencing and multiome data to identify neuronal mitochondrial gene suppression as a driver of Alzheimer's dementia, revealing genetic and epigenetic mechanisms underlying cognitive resilience.

Neuronal Hyperactivity Induces Tau Phosphorylation Selectively in Excitatory Pyramidal Neurons Which Contributes to GluA2 Regulation

This study shows that neuronal hyperactivity selectively increases tau phosphorylation at S202/T205 in excitatory hippocampal neurons, which reduces GluA2 surface expression and may contribute to Alzheimer's disease pathology.

High-content imaging of live microglia-containing Alzheimer's disease brain organoids

This study uses microglia-containing Alzheimer's disease brain organoids to monitor Aβ aggregation and cellular viability, identifying age-dependent disease-associated phenotypes.

Repeated VU0155069 Treatment Is Associated with Region- and Pathological Stage-Specific Dendritic Spine Remodeling in Female 3xTg-AD Mice

This study shows that repeated VU0155069 treatment causes region- and stage-specific dendritic spine remodeling in female 3xTg-AD mice, affecting multiple brain circuits.

Genedex: Contextualizing gene signatures across Alzheimer's disease pathology, cell types, and brain regions

Genedex integrates gene signatures from Alzheimer's disease studies to contextualize gene expression across pathology, cell types, and brain regions, revealing new insights into disease mechanisms.

Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias

The paper systematically adjudicates genetic evidence for Alzheimer's disease and related dementias, identifying 111 high-confidence loci through a tiered framework applied to large-scale genome-wide studies.

Amyloid Folding: an Origami-Based Approach

The paper introduces an origami-based model to visualize amyloid beta-sheet structures and their topological arrangements, aiding in teaching amyloid folding and related concepts.

New Insights on Bridging Integrator 1 Protein Isoforms as a Risk Increasing Gene in Alzheimer's Disease

The paper identifies BIN1 isoform expression patterns and genetic variants associated with Alzheimer's disease risk using GWAS and hiPSC differentiation data.

TMEM55B downregulation promotes neurodegeneration in Alzheimer disease models.

The paper shows TMEM55B downregulation contributes to neurodegeneration in Alzheimer's disease models by impairing lysosomal transport and autophagy.

Alzheimer's Disease-Associated Proteomic Changes in Olfactory Stem Cells Show Pathway-Level Transcriptomic Overlap

This study identifies proteomic and transcriptomic changes in olfactory stem cells from AD and MCI patients, revealing pathway-level overlaps and potential biomarkers.

Astrocytic ablation of truncated TrkB receptors reduces amyloid plaques and prevents synaptic loss in 5xFAD mice

This study shows that reducing TrkB.T in astrocytes reduces amyloid plaques and prevents synaptic loss in 5xFAD mice by enhancing BDNF-TrkB.FL signaling.

Temporal Proteomics Links the APP London Mutation to Early Cholesterol Remodeling Cell Programs in Human Neurons

The paper uses proteomic analysis of APP-London mutant neurons to show early cholesterol remodeling and altered A beta secretion without changes in total cholesterol.

Early Insulin Signaling Defects and Oxidative Stress Kinase Activation Precede Tau Pathology in PS19 Tau Transgenic Mice

A coordinated and reproducible multicellular response to AD pathology

The paper identifies robust multicellular axes associated with Alzheimer's disease pathology and sex using single-cell data from 427 donors, validated in an independent dataset.

Multivalent ubiquitin recognition regulates multiple stages of Tau self-assembly

This study identifies multivalent ubiquitin recognition as a regulator of Tau self-assembly stages, showing ubiquitin's role in modulating condensate formation and aggregation.

Q-DOAS: A Proximity Quenching Assay for Real-Time Detection of Early Protein Aggregation Events

Q-DOAS detects early protein aggregation events in real time using a proximity-quenching assay, providing quantitative data for studying neurodegenerative diseases.

Discovery of a brain-penetrant CHI3L1 inhibitor as an oral modulator of neuroinflammation in Alzheimers disease

This paper identifies DELC2, a brain-penetrant CHI3L1 inhibitor, which reduces neuroinflammation and amyloid-β levels in Alzheimer's disease models.

Spatial proximity to AD pathology defines cell-type and genotype-specific characteristics in human AD hippocampus

The paper analyzes spatial relationships between AD pathology and gene expression in human hippocampus using MERFISH and snRNA-seq data, identifying cell-type and genotype-specific effects of A{beta} and tau pathology.

Design of readers for pathological PTM proteoforms in Alzheimer's disease

The paper designs and validates protein readers that specifically detect disease-related modifications in Tau and Abeta in Alzheimer's disease models and human samples.