Alzheimer's disease research and treatments

Neuronal APOE4 alone is sufficient to drive tau pathology, neurodegeneration, and neuroinflammation in an Alzheimer's disease mouse model

This study shows neuronal APOE4 alone can drive tau pathology, neurodegeneration, and neuroinflammation in a mouse model, similar to a human APOE4 knock-in model.

Serum Lipidome as an Early Peripheral Indicator in Familial Alzheimers Disease

The paper identifies a serum lipidomic signature in asymptomatic Alzheimer's disease mutation carriers that differentiates them from non-carriers and correlates with dementia risk factors.

Fus depleted oligodendrocytes reduce neuronal damage and attenuate AD progression in the AppNL-G-F mouse

The paper shows that enhancing oligodendrocyte function in a mouse model of Alzheimer's Disease reduces neuronal damage and slows disease progression.

Pathological tau alters head direction signaling and induces spatial disorientation

This study shows that pathological tau expression in the anterodorsal thalamic nucleus disrupts head direction signaling, leading to spatial disorientation in mice.

ApoE4 accelerates the condensate to amyloid transition of tau

This study shows apoE4 accelerates tau condensate to amyloid transition, while lipidation reduces its effects, suggesting lipidation enhancement could counteract its pathogenic role.

ACUTE AMYLOID-B 40 EXPOSURE DISRUPTS METABOLIC INSULIN SIGNALING IN BLOOD-BRAIN BARRIER ENDOTHELIAL CELLS

This study shows that Aβ40 exposure disrupts insulin signaling in BBB endothelial cells by reducing Akt phosphorylation and altering AMPK activity.

Nanobodies targeting hnRNPA2/B1 and tau

The paper develops nanobodies targeting hnRNPA2/B1 and tau, showing they colocalize with targets and can reduce protein levels when fused to ubiquitin ligase domains.

Blood-based Transcriptomics Reveal Sex- and Amyloid-Modulated Biology of Plasma pTau217 in Preclinical Alzheimer's Disease

The paper identifies gene associations with plasma pTau217 in preclinical Alzheimer's disease, showing modulation by APOEε4, Aβ-PET, and sex, with X-linked genes playing a role.

Graded regulation of microtubule-binding of Tau by the phosphorylation state of the proline-rich region in living neurons

This study investigates how phosphorylation patterns in the proline-rich region of Tau affect its microtubule-binding dynamics in neurons using FRAP and computational modeling.

APOE E4 Alzheimer's Risk Converges on an Oligodendrocyte Subtype in the Human Entorhinal Cortex

The paper investigates how APOE genotype affects gene expression in the human entorhinal cortex, identifying an oligodendrocyte subtype as a potential mediator of Alzheimer's disease risk.

ApoE lipidation, not isoform, is the key modulator of Aβ interaction, uptake, and cytotoxicity

This study shows that ApoE lipidation, not isoform, most strongly affects Aβ interaction, uptake, and cytotoxicity in astrocytes.

Single-cell Spatial Transcriptional Profiling Uncovers Heterogeneous Cellular Responses to Pathogenic Tau in a Mouse Model of Neurodegeneration

The paper uses single-cell spatial transcriptomics to analyze tau pathology in mouse brains, revealing cell-autonomous and non-autonomous effects of tau accumulation on gene expression and pathways.

Super-Resolution Imaging Uncovers Nanoscale Tau Aggregate Hyperphosphorylation Patterns in Human Alzheimers Disease Brain Tissue

The paper uses super-resolution imaging to analyze nanoscale tau aggregates in AD and PART brain tissues, revealing hyperphosphorylation patterns and morphological differences.

Tau oligomers can occur in human brains within days of a single traumatic brain injury

This study identifies tau oligomers in the brains of individuals who died shortly after traumatic brain injury, suggesting an early pathological mechanism linked to Alzheimer's disease.

Energetic profiling reveals thermodynamic principles underlying amyloid fibril maturation

The paper uses energetic profiling on cryo-EM data to uncover thermodynamic principles governing amyloid fibril maturation and polymorphic divergence.

Amyloid Beta Glycation Induces Neuronal Mitochondrial Dysfunction and Alzheimers Pathogenesis via VDAC1-Dependent mtDNA Efflux

This paper shows that glycated amyloid-beta causes mitochondrial dysfunction and Alzheimer's pathology by triggering the cGAS-STING pathway via VDAC1-dependent mtDNA release.

Dephosphorylation of YES kinase-mediated co-chaperone DNAJB6b phosphorylation attenuates tau protein aggregation

The paper investigates how phosphorylation of DNAJB6b by YES kinase affects tau protein aggregation in Alzheimer's disease, suggesting it may contribute to disease risk and identify a potential biomarker.

Meningeal vascular Aβ deposition associates with cerebral hypoperfusion and compensatory collateral remodeling

This study shows that Aβ deposition in meningeal arteries correlates with reduced cerebral blood flow and collateral vessel remodeling in a mouse model of AD, with sex differences in Aβ burden.

Porosome reconstitution reverses Alzheimers in human brain organoids

This paper demonstrates that porosome reconstitution with apigenin reverses Alzheimer's features in human brain organoids by repairing synaptic and metabolic defects.

Single-nucleus multi-omics identifies shared and distinct pathways in Pick's and Alzheimer's disease

This study uses single-nucleus multi-omics to identify shared and distinct regulatory pathways in Pick's and Alzheimer's disease, revealing disease-specific enhancers and TF binding patterns.

APOE4-Aβ synergy drives brain network dysfunction and neuronal lysosomal-ER proteostasis dysregulation in preclinical Alzheimer's disease

This study investigates how APOE4 and Aβ interact in preclinical Alzheimer's disease, finding their synergistic effects on neuronal proteostasis and network dysfunction.

Olfactory biopsy analysis of Alzheimer's pathobiology across disease stages

The paper analyzes olfactory biopsy samples from AD patients and pre-clinical stages using scRNA-seq to identify neuroinflammatory changes detectable in early disease.

Investigating the Effects of APOE Genotype on Intracellular Cholesterol and the Endolysosomal System in the Aging Mouse Brain

This study investigates how APOE genotype, sex, and aging affect intracellular cholesterol and the endolysosomal system in mouse brains, revealing region-specific and sex-dependent changes in APOE4 mice.

Longitudinal investigation of spatial memory and retinal parameters in a 5xFAD model of Alzheimers disease reveals differences dependent on genotype and sex

The paper investigates retinal parameters and spatial memory in 5xFAD mice, finding sex-based differences and correlations between retinal layer thickness and memory performance.

DEER of Singly Labelled Proteins to Evaluate Supramolecular Packing of Amyloid Fibrils

This study introduces DEER spectroscopy to analyze the supramolecular packing of amyloid fibrils, showing that heparin-induced fibrils are mispacked while seeded aggregation improves packing order.

Aβ-targeting synNotch Receptor for Alzheimer's Disease: Expanding Applications to Extracellular Protein Aggregates

This paper demonstrates that a synNotch receptor can target extracellular Aβ aggregates, enabling the production of AD therapies like Lecanemab and Aducanumab in response to these aggregates.

Increased levels of HAPLN2, which anchors dense extracellular matrix, in the hippocampus of APOE4 targeted replacement mice

The paper identifies increased HAPLN2 levels in APOE4 mice hippocampus, linking it to extracellular matrix changes and potential Alzheimer's disease risk.

Functional Effects of CD33 SNP rs12459419 on Microglial Gene Regulation and Alzheimer's Disease Risk

This study investigates how the CD33 SNP rs12459419 affects microglial gene regulation and Alzheimer's disease risk by analyzing multiple genomic datasets.

L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer's synaptic deficits

This study identifies L-fucose as a monosaccharide neuromodulator that enhances synaptic function and mitigates Alzheimer's disease symptoms in mice.

Proximity labeling of the Tau repeat domain enriches RNA-binding proteins that are altered in Alzheimer's disease and related tauopathies

The paper identifies RNA-binding proteins interacting with tau's repeat domain using proximity labeling, showing their enrichment in Alzheimer's and tauopathies.