Alzheimer's disease research and treatments

Composition and activity of the proteasome in human iPSC-derived neuronal model of early-stage sporadic Alzheimer's disease

The paper examines proteasome composition and activity in human iPSC-derived cortical neurons from early-stage sporadic Alzheimer's disease patients, finding increased 20S proteasome assemblies and proteolytic activity.

Cerebrovascular Single-Nucleus RNA-Seq Reveals Heat Shock Activation and Vascular Remodeling in Alzheimer's Disease and Primary Tauopathies

The paper uses single-nucleus RNA-seq to analyze cerebrovascular transcriptomic changes in Alzheimer's Disease and primary tauopathies, identifying shared heat-shock responses and disease-specific vascular remodeling.

Intrinsic molecular susceptibility underlies selective neuronal vulnerability in the Alzheimer's disease entorhinal cortex

The paper identifies intrinsic molecular features of calbindin-expressing neurons in the entorhinal cortex that contribute to their vulnerability in Alzheimer's disease and suggests potential therapeutic targets.

Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) features CTE-like tau seeds in brain and spinal cord

This study identifies CTE-like tau seeds in ALS/PDC brain and spinal cord using alanine mutational scanning, suggesting ALS/PDC is a CTE-like tauopathy.

A pocket-centric framework for selective targeting of amyloid fibril polymorphs

The paper analyzes 400 cryo-EM structures of amyloid fibrils to identify shared and unique surface pockets, showing pocket-level convergence across polymorphs and proteins, and proposes a framework for selective ligand targeting.

TDP-43 subtypes shape transcriptomic signatures in Alzheimer's disease

The paper decouples TDP-43 and Tau pathology in Alzheimer's disease by analyzing transcriptomic profiles and identifies subtype-specific transcriptional signatures.

Early Binding of Anti-Amyloid Antibodies to CAA Drives Complement Activation, Inflammation and ARIA in Mice

This study investigates how early binding of anti-amyloid antibodies to cerebral amyloid angiopathy (CAA) drives complement activation, inflammation, and ARIA in Alzheimer's disease mouse models.

Patient cerebral organoids capture Alzheimers disease proteomic biomarkers and drug targets

The paper benchmarks proteomic biomarkers and drug targets in patient-derived cerebral organoids against clinical cohorts, finding they detect most candidates and replicate disease changes in a quarter of reproducible markers.

Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology

This study identifies imidazole propionate as a gut bacterial metabolite linked to Alzheimer's disease pathology through human and mouse experiments.

Sexually dimorphic behavioural signatures of tau toxicity in adult Drosophila

This study establishes an adult-onset Drosophila model of tauopathy, revealing sex-specific effects on survival and behavior and identifying genetic modifiers of tau-induced dysfunction.

Virus-mediated tau aggregate seeding in a cellular model

This study shows that tau aggregates can be packaged into lentiviral particles and induce tau aggregation in recipient cells, suggesting a potential mechanism linking viral infections to neurodegenerative diseases.

Association of cytochrome c oxidase dysfunction with amyloidosis in Alzheimer's disease and patient-derived cerebral organoids

The paper identifies CCO subunit loss and reduced CCO activity in AD brains and shows pharmacological CCO inhibition promotes amyloid production in cerebral organoids.

ABCA7 rs3752231 variant effects on glial responses to amyloid-β and plaque maturation in Alzheimer's disease.

This study examines the effect of the ABCA7 rs3752231 variant on glial responses to amyloid-β and plaque maturation in Alzheimer's disease using post-mortem brain data and single-nucleus RNA sequencing.

Targeted Photodegradation of Misfolded Proteins via Self-photosensitizing with Molecularly Produced Light

This study demonstrates that molecularly produced light from ADLumin-5 can degrade misfolded proteins like beta-amyloid and reduce their toxicity in vitro and in vivo.

A multi-organ spatial metabolomic atlas of exercising mice reveals neuronal Complex I as a convergent and sufficient axis for tau pathology reduction in PS19

This paper constructs a spatial metabolomic atlas of exercise in mice, identifies Complex I as a key target for reducing tau pathology, and shows that enhancing its activity mimics exercise's protective effects.

Molecular mechanisms underlying amyloid lowering by aducanumab: differential and comparative effects of sex and IgG reveal the post-treatment disease brain

This study examines the molecular effects of aducanumab treatment in 5XFAD mice, revealing sex-dependent and IgG-mediated changes in amyloid and associated pathways.

Pore-Resolved High-Throughput Quantification of Amyloid Aggregation and Amplification

This paper introduces APQ, a pore-resolved platform for quantifying amyloid aggregation and amplification, revealing population-level structural insights beyond conventional ThT assays.

Early oligodendrocyte dysfunction signature in Alzheimer's disease: Insights from DNA methylomics and transcriptomics

The paper identifies an oligodendrocyte DNA methylation signature in Alzheimer's disease that is preserved across brain regions and disease stages, and is associated with altered gene expression in OLGs.

An Integrated Framework for Transcriptomic Characterization and Lorentzian Hyperbolic Visualization of a High-Risk Topological Branch in Alzheimer's Disease

The paper develops an analytical framework to characterize transcriptomic variation in a high-risk topological branch of Alzheimer's disease and introduces Lorentz t-SNE for hyperbolic visualization of transcriptomic data.

Mitochondrial Complex I Modulator Restores Network Resilience in Advanced Alzheimer's Disease Through Metabolic Reprogramming

The paper shows that modulating mitochondrial complex I in advanced Alzheimer's disease improves metabolic resilience through coordinated mitochondrial and lipid metabolism.

AI-Guided Discovery of Small Molecule LILRB4 (ILT3) Inhibitors Reprograms Microglia and Reduces Amyloid Pathology

This paper identifies small molecule inhibitors of LILRB4 that reduce amyloid pathology and improve cognition in a mouse model of Alzheimer's disease.

The genetic architecture of dementia risk: how Alzheimer's disease vulnerability converges on lipid metabolism and immune cell networks

This paper maps dementia risk genes across tissues and cell types using HPA GeneSet Explorer, revealing convergent neuronal enrichment and disease-specific modules in Alzheimer's, Lewy body, and Frontotemporal dementias.

MicroRNA-181 influences Alzheimer's risk by regulating neprilysin and microtubule-associated tau pathways, offering a novel target

The paper identifies miR-181's role in regulating neprilysin and tau pathways linked to Alzheimer's risk, suggesting it as a novel therapeutic target.

Prenatal Alcohol Exposure Disrupts γ-Secretase Activity and Impairs Learning and Memory in Wild-Type and 3xTg-AD Mice

This study shows that prenatal alcohol exposure disrupts γ-secretase activity and leads to learning and memory impairments in both wild-type and 3xTg-AD mice.

Loss of endogenous tau suppresses APOE4-induced patterned behavioral decline and axon dysmorphia in a C. elegans model of Alzheimers disease

This study shows that reducing endogenous tau in C. elegans mitigates APOE4-induced behavioral and axonal defects, suggesting a role for tau in AD-related neurodegeneration patterns.

Utilizing a cell culture based novel cellular thermal shift assay to understand the isoform-dependent thermal stability of ApoE variants

The paper develops BiTSA, a bioluminescence-based thermal stability assay, to characterize isoform-dependent thermal stability of ApoE variants in living cells and confirms that ApoE4 is less stable than ApoE3 in native tissue.

TOMM40 '523' genotype induces sex- and tissue- specific differences in cholesterol and triglyceride levels in an APOE-TOMM40 humanized mouse model

The paper investigates how TOMM40 523 poly-T variants affect lipid levels and AD biomarkers in a humanized mouse model, finding sex- and tissue-specific differences.

APOE interacts with COX-2 on lipid droplets to modulate inflammatory lipid signaling

This study identifies APOE interacting with COX-2 on lipid droplets, showing APOE3 promotes and APOE4 suppresses COX-2 activity and prostaglandin production.

Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease

The paper identifies preserved mitochondrial bioenergetics in asymptomatic Alzheimer's disease brains and suggests NAD+ precursor interventions could maintain cognitive function despite pathology.

Structural Mechanism and Cellular Restriction of Tau Seeding from Endolysosomes

This study investigates the role of lysosomal components in tau seeding and finds that the PITT pathway and VPS13C are strongly involved in tau spread, while CASM and ALG-2 have more limited roles.