Alzheimer's disease research and treatments

From DNA-Encoded Library (DEL) Screening to In Vivo Validation: LILRB4 (ILT3)-Targeted Small Molecules Reprograms Myeloid Immune Suppression

This study identifies APX1 as a small molecule that targets LILRB4, modulating microglial immune suppression and improving AD symptoms in a mouse model.

Astrocyte subtype-specific expression of the sodium-coupled citrate transporter SLC13A5 and citrate metabolism genes across Alzheimer's disease pseudoprogression: a single-nucleus RNA sequencing analysis of the human middle temporal gyrus

Proteomic signatures of cognitive resilience in LOU/c/Jall rats converge with inverse hippocampal axes of Alzheimer disease.

The paper identifies proteomic differences in the hippocampus of LOU/c/Jall rats associated with cognitive resilience, finding patterns opposing those seen in Alzheimer's disease.

Synaptic plasticity deficits via aberrant engagement of metaplasticity in the hippocampus of PS19 mice

This study examines synaptic plasticity and neuroinflammation in the hippocampus of PS19 mice, revealing region-specific synaptic deficits and altered metaplasticity.

Quantitation of Spatial Proteoforms in Alzheimer's Disease

The paper quantifies spatial proteoforms in Alzheimer's disease by analyzing subcellular protein localization and identifies key pathways disrupted in disease progression.

Retinal Transcriptome-Wide Association Study Identifies Novel Alzheimer's Disease Risk Genes

This study identifies 62 Alzheimer's disease-associated genes using retinal transcriptome-wide association studies and validates 31 in an independent cohort, highlighting immune dysregulation and novel risk genes.

An open dataset of cerebral tau deposition in young healthy adults based on MK6240 positron emission tomography

The paper presents an open dataset of cerebral tau deposition in young healthy adults using [18F]MK6240 PET to support imaging biomarker studies in non-geriatric populations.

The 329HHK331 motif is essential for Alzheimer's disease tau filament fold

The paper investigates the role of the 329HHK331 motif in Alzheimer's disease tau filament formation and shows that mutations in this region affect filament structure and seeding activity.

The NORAD-pumilio regulatory axis links lncRNA dysregulation to tau propagation-associated phenotypes

The paper identifies lncRNA dysregulation in MAPT mutation carriers and shows the NORAD-pumilio axis modulates tau propagation.

HnRNPAB-targeted antisense oligonucleotides ameliorate tau pathology and cognitive deficits by modulating Alzheimers disease-associated alternative splicing

This study identifies AB332, a hnRNPAB isoform, as a repressor of MAPT exon 10 inclusion and shows that targeting hnRNPAB with antisense oligonucleotides reduces tau pathology and cognitive deficits in AD mice.

Neuropathological and Functional Impact of Astrocyte-Derived Extracellular Vesicles in an Aged Model of Alzheimer's Disease

This study shows that astrocyte-derived extracellular vesicles from cognitively impaired individuals promote tau accumulation in an Alzheimer's mouse model, suggesting they may be both biomarkers and drivers of neurodegeneration.

Humanized tauopathy chimeras uncover microglial and lncRNA strategies for neuroprotection

The paper develops a humanized neuroimmune model to study tauopathy and identifies microglial and lncRNA mechanisms that protect neurons.

Multiregional single-cell profiling reveals shared and specialized cellular vulnerability in Alzheimer's disease

This study uses single-nucleus RNA-seq, ATAC-seq, and Multiome to analyze Alzheimer's disease across multiple brain regions, revealing shared and region-specific cellular vulnerabilities.

Zinc Differentially Modulates Tau Aggregation, Fibril Morphology, and Prion-like Seeding in a Construct-Dependent Manner

This study shows zinc modulates tau aggregation and seeding differently based on tau sequence context, highlighting cofactor effects depend on sequence and conformational constraints.

Complex coacervation reshapes the aggregation landscape of tau

This study shows that complex coacervation changes tau aggregation by redirecting it to a distinct kinetic regime and altering amyloid properties.

Charge-Driven Fibril Recognition and Covalent Disruption of Aβ42 byPaddlewheel Diruthenium Complexes

This study uses atomistic simulations to show how charge changes in diruthenium complexes affect their interaction with Aβ42 fibrils, enhancing fibril disruption through electrostatic tuning.

Alzheimer's Disease-Related Mutations in APP Influence Colorectal Tumor Formation in a Sex-Dependent Manner

This study shows that Alzheimer's disease-related APP mutations promote colorectal tumor formation in male mice but inhibit it in female mice, with sex-dependent transcriptomic and immune differences.

Pharmacodynamic and stage-dependent therapeutic efficacy of SFRP1 neutralization in a mouse model of Alzheimer s disease

This study evaluates the therapeutic efficacy of SFRP1 neutralization at different disease stages in a mouse model of Alzheimer's disease, finding that early intervention is most effective.

Tau pSer396 and pSer404 Define Distinct Epitope Regions Linked to Different Antibody Functions

The paper compares pSer396- and pSer404-selective antibodies, showing differences in efficacy and structural binding modes, and highlights how humanization affects their therapeutic properties.

CD33 and Clusterin Interact Biophysically and Genetically to Modulate Alzheimer Risk

This study shows how non-coding variants in CD33 affect Alzheimer's risk by altering CD33M dimerization and interactions with clusterin and Aβ, impacting microglial function.

Humanized APP is the primary determinant of regional brain volume in humanized APOE knock-in mice: a cross-sectional ex vivo MRI study

This study uses MRI to show that humanized APP significantly reduces brain volume in humanized APOE knock-in mice, with hAPOE4 homozygosity exacerbating this effect.

APP-CTFβ/C99 oligomers drive synaptic vesicle tethering through C-terminal interactions

The paper shows that APP-CTFβ oligomers enhance synaptic vesicle tethering and release through C-terminal interactions, contributing to neuronal hyperactivity.

Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation

The paper uses proteomic analysis in ApoE knock-in mice to show sex-dependent differences in proteostasis regulation by ApoE isoforms, with ApoE4 showing early metabolic and mitochondrial changes.

FAD mutations suppress brain angiogenesis and neuroprotection by reducing γ-secretase processing and dimerization of VEGFR2.

This study shows FAD mutations reduce VEGFR2 dimerization and downstream angiogenesis and neuroprotection by increasing VCTF1 accumulation.

Investigating a Relation between Amyloid Beta Plaque Burden and Accumulated Neurotoxicity Caused by Amyloid Beta Oligomers

This paper develops a mathematical model to simulate Aβ dynamics and quantify accumulated neurotoxicity as a marker of biological age, showing its non-linear relationship with plaque burden and the impact of degradation efficiency.

Injury-induced tau pathology promotes aggressive behavior in Drosophila without neurodegeneration.

This study shows that injury-induced tau phosphorylation in Drosophila leads to aggressive behavior through dopaminergic circuit activation without causing neurodegeneration.

Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer's disease and related dementias in a multi-site autopsy cohort

This paper performs a large-scale GWAS meta-analysis of neuropathologic lesions in Alzheimer's disease and related dementias, identifying both known and novel genetic associations.

Arc mediates intercellular tau transmission via extracellular vesicles

This study identifies Arc as critical for packaging tau into extracellular vesicles, facilitating its release and intercellular transmission in Alzheimer's disease.

The CHIP-LMO7-BAG5 complex controls tau clearance and yields repurposed and newly designed therapeutic candidates for Alzheimer's disease

The paper identifies the CHIP-LMO7-BAG5 complex as a regulator of tau clearance and develops therapeutic candidates targeting this complex for Alzheimer's disease.

Anti-amyloid immunotherapy drives APOE4 specific increases in glial reactivity, perivascular immune activation, and ARIA-like events

This study investigates how anti-amyloid immunotherapy affects APOE4 carriers, showing increased glial reactivity, perivascular immune activation, and ARIA-like events.