Alzheimer's disease research and treatments

Autonomous AI-Driven Nanoscale Spatial Mapping Reveals Novel Targets and Ternary Architectures in 5xFAD Alzheimer's Disease Model

The paper uses AI to analyze spatial data from Alzheimer's mouse models, revealing new protein interactions and synaptic structures linked to disease.

The protein and lipid compositions of brain apolipoprotein E particles are cell type-specific

The paper identifies cell type-specific lipid and protein compositions of apoE lipoproteins secreted by different brain cell types and found in cerebrospinal fluid.

Cell type-specific histone acetylation landscape in Alzheimer's disease reveals a putative role of MITF in microglia

This study identifies cell-type-specific histone acetylation changes in Alzheimer's disease, highlighting MITF's potential role in microglial dysfunction.

Tau-induced elevation in promoter-proximal RNA polymerase II pausing is linked to decreased expression of long neuronal genes in a Drosophila tauopathy model.

The paper investigates how pathological tau affects gene expression in a Drosophila tauopathy model, finding increased RNA polymerase II pausing linked to reduced expression of long neuronal genes.

Ion modulation restores local synaptic function in APOE4 neuronal networks despite persistent impairments in global network organization

Soluble pathogenic tau transmission to astrocytes drives acute oxidative damage, cellular senescence, and neurovascular uncoupling in a model of Alzheimers tauopathy

This study shows that soluble pathogenic tau aggregates are transmitted to astrocytes, causing mitochondrial dysfunction, senescence, and neurovascular uncoupling in a tauopathy model.

Quantitative Modelling of Amyloid-β Dynamics in Brain, CSF, and Plasma During Sleep and Wakefulness

The paper models A{beta} dynamics across brain, CSF, and plasma during sleep and wakefulness, showing increased CSF A{beta}42 levels after sleep due to sampling effects and impaired clearance.

Targeted dephosphorylation of Tau at the endogenous level promotes its association with microtubules.

This study shows targeted dephosphorylation of phospho-Tau at the endogenous level promotes its association with microtubules.

A scalable human neuron model of Alzheimer's disease relevant tauopathy reveals mechanisms linking Tau fibrillization to synaptic dysfunction

This paper develops scalable human neuron models of Alzheimer's disease to reveal mechanisms linking Tau fibrillization to synaptic dysfunction and identifies therapeutic targets.

Progressive behavioral and cognitive decline in Drosophila harboring AD-associated APOE4 variants

This study shows that Drosophila with APOE4 variants exhibit AD-like phenotypes under stress and metabolic challenges, supporting a multi-hit model of disease.

Differential Effects of Neutral Sphingomyelinase and Serine Palmitoyltransferase Inhibitors on Alzheimer's-Like Neuropathology.

This study compares the effects of nSMase and SPT inhibitors on Alzheimer's-like pathology in mice, finding that nSMase inhibition reduces neuropathology while SPT inhibition worsens it.

APOE 4/4 promotes dysfunctional and inflammatory phenotypes concomitant with impaired maturation of hiPSC-derived astrocytes

This study shows that APOE 4/4 genotype leads to dysfunctional and inflammatory astrocytes with impaired maturation and altered glutamate/Aβ handling in hiPSC-derived cultures.

Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease

This study shows that C4 deficiency reduces amyloid plaques and neuroinflammation in a mouse AD model, suggesting C4's role in glial reactivity and pathology.

Characterization of the knock-in AppSAA mouse model as a powerful tool for Alzheimer's disease preclinical research.

The paper characterizes the AppSAA knock-in mouse model, showing it recapitulates age-dependent Alzheimer's disease phenotypes and provides a tool for preclinical research.

Cyclic Peptides Target CAPON and Modulate Cellular Responses under Alzheimers Disease-Relevant Stress

This study identifies cyclic peptide ligands targeting CAPON, showing reduced neuronal toxicity and tau phosphorylation under Alzheimer's disease stress conditions.

Rare extreme polygenic risk scores strongly indicate Alzheimer's disease risk

The paper identifies individuals with extreme polygenic risk scores (PRS) for Alzheimer's disease (AD) and shows they have significantly elevated AD risk across multiple ancestries and APOE diplotypes.

DNAJB6b: a complete amyloid inhibitor

This study investigates how DNAJB6b binds to Aβ42 fibrils and inhibits amyloid elongation, providing a quantitative mechanism for its role in suppressing amyloid formation.

mTOR drives cerebrovascular dysfunction and blood-brain barrier breakdown in a model of Alzheimers disease with cerebral amyloid angiopathy

This study shows that mTOR inhibition reduces cerebrovascular Aβ accumulation and improves cognitive function in a mouse model of Alzheimer's disease with cerebral amyloid angiopathy.

Aβ-42 sidechain deamidation at Q15 or N27 modulates protein aggregation and alters microglial cytokines and CD68

This study investigates how deamidation at Q15 or N27 in Aβ-42 affects its aggregation and microglial immune response, finding reduced inflammation and altered CD68 expression.

The sphingosine-1-phosphate receptor functional antagonist fingolimod exacerbates neuroinflammation and tau pathology in a mouse model of tauopathy

This study shows that fingolimod worsens T cell infiltration and tau pathology in a mouse model of tauopathy, despite reducing peripheral T cells.

ApoE4 impairs astrocyte lipid droplet formation via endolysosomal dysfunction

This study shows ApoE4 impairs astrocyte lipid droplet formation by disrupting endolysosomal function and demonstrates that PCSK9 can restore lipid droplet formation by preventing ApoE4 internalization.

Rapid Mechanistic Bridging of an Alzheimer's Disease Plasma Protein Staging Panel Across Brain Proteomics Cohorts

The paper evaluates a seven-protein plasma panel across brain proteomics cohorts to show its association with AD proteomic changes.

Multi-site Cleavage of Amyloid-β by a Minimal 5-mer Catalytic Peptide: Mimicking Serine Protease Activity via Hydrophobic Anchoring

This study investigates how the pentapeptide SKGQA cleaves multiple sites on amyloid-beta by using hydrophobic anchoring and stochastic catalytic targeting.

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

This study identifies a consistent proteomic signature of APOE ε4 across plasma and CSF, revealing cell-type-specific molecular effects in brain tissues associated with Alzheimer's disease risk.

Aberrant neuronal cell cycle re-entry induces late-onset Alzheimer's disease relevant neuropathological and gene expression changes

This study shows that modulating neuronal cell cycle re-entry at a later age prevents Alzheimer's disease-related pathologies and highlights its relevance to late-onset AD.

High-Throughput Screening Identifies Small-Molecule Inhibitors of the Tau-LRP1 Interaction

This study identifies small-molecule inhibitors of the tau-LRP1 interaction using biochemical assays and high-throughput screening, showing reduced tau uptake in cellular assays.

Structure and epitope mapping of the conformational anti tau antibody DC11

This study determines the structure of the DC11 antibody and maps its epitope on truncated tau proteins using crystallography and computational methods.

Melanin Suppresses Aβ Aggregation and Toxicity

This study shows melanin suppresses Aβ42 aggregation and toxicity in vitro and in a cell model, suggesting potential therapeutic applications for Alzheimer's disease.

Tau isoforms modulate the axon initial segment controlling axonal trafficking and neuronal excitability

This study shows that tau isoform balance regulates axon initial segment maturation, excitability, and transport, linking cytoskeletal organization to neuronal function.

Pathogenic tau in the mouse locus coeruleus induces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimers disease

This study shows that pathogenic tau in the locus coeruleus causes hyperactivity and neuropsychiatric symptoms similar to early Alzheimer's disease in mice.