Alzheimer's disease research and treatments

Identification of functional non-coding variants affecting Alzheimer's disease risk by Massively Parallel Reporter Assay

The paper identifies functional non-coding variants affecting Alzheimer's disease risk using MPRA and validates their effects through CRISPR/Cas9.

In vitro comparison of Aβ-targeting SNIPR, synNotch, and TRUCK for cell-based drug delivery in Alzheimer's disease.

The paper compares SNIPR, synNotch, and TRUCK systems for Aβ-targeting cell-based drug delivery in Alzheimer's disease, finding SNIPR and synNotch outperform TRUCK in therapeutic response.

Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer's disease

Selective reduction of KCNA4 in vulnerable glutamatergic-serotonin neurons of the dorsal raphe nucleus in Alzheimers Disease

The paper investigates how selective reduction of KCNA4 in 5HT/glut neurons of the dorsal raphe nucleus contributes to tau pathology and depressive-like behaviors in Alzheimer's disease.

Taurine Inhibits Apolipoprotein E4 Aggregation

This study shows taurine inhibits ApoE4 aggregation and reduces its pathophysiological effects, similar to tramiprosate and 3-sulfopropanoic acid.

Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models

This study identifies SHIP1 ligands with brain exposure and in vivo activity in Alzheimer's models, showing target engagement and reduced neuroinflammation.

Poly(lactic-co-glycolic acid) immunomodulatory nanoparticles attenuate neuroinflammation and Alzheimer's disease-related pathology in 5xFAD mice

A Unifying Mechanism for Synaptic Amyloid beta Toxicity Beta Adrenergic Potentiation of the Ca2+ Channel CaV1.2 by Amyloid beta

This paper identifies a mechanism by which amyloid beta potentiates CaV1.2 channels via β2AR, leading to synaptic dysfunction and neurotoxicity, and shows that disrupting this pathway prevents these effects.

Spatial Single-Cell Proteomics Reveals Molecular Trajectories Of Tangle-Bearing Neurons In Alzheimer's Disease

The paper uses spatial single-cell proteomics to analyze tangle-bearing neurons in Alzheimer's disease, revealing a continuum of proteomic changes associated with tau pathology.

Development of Potent and Cell Active 5-Azaindole-Based Tau Tubulin Kinase Inhibitors

This study develops and characterizes a potent and cell-active inhibitor of TTBK1 and TTBK2, with selectivity and potential therapeutic applications for neurodegenerative diseases.

PSEN1 mutant marmoset fibroblasts mimic multi-omic signatures of Alzheimer's disease

This study shows that PSEN1 mutant marmoset fibroblasts exhibit multi-omic signatures similar to Alzheimer's disease in humans, highlighting sex-specific differences and disease-relevant pathways.

N-terminally acetylated Met11-Tau: a new pathological truncated Tau species with functional relevance in Alzheimer Disease

This study identifies and characterizes a novel N-terminally acetylated Tau variant that accumulates in AD models and patients, exacerbates pathology, and is a potential therapeutic target.

Amyloid plaques drive state-dependent long-range circuit reorganization in the hippocampus

This study shows amyloid plaques in the hippocampus cause long-range circuit reorganization in freely behaving mice, affecting place cell distribution and functional maps.

Genetic drivers of progression in Alzheimers disease are distinct from disease risk

The paper identifies genetic factors associated with Alzheimer's disease progression using GWAS and longitudinal data, finding distinct genetic drivers from disease risk.

Multi-omic phenotyping of MAPT V337M neurons reveals early changes in axonogenesis and tau phosphorylation

The paper uses multi-omic analysis to study MAPT V337M neurons, finding altered axonogenesis and tau phosphorylation, with p38 MAPK pathway involvement in tau phosphorylation in V337M neurons.

Sleeve gastrectomy improves metabolic health, cognition, and Alzheimer's Disease pathology in 3xTG mice

This study shows that sleeve gastrectomy improves metabolic health, cognition, and Alzheimer's pathology in 3xTg-AD mice by modulating autophagy and insulin signaling.

D-Methionine Improves Spatial Navigation and Attenuates Oxidative Stress and Amyloid Pathology in a Sex-Specific Manner

This study shows that D-methionine improves spatial memory and reduces amyloid pathology and oxidative stress in AD mouse models, with sex-specific effects.

Glucose hypometabolism and hyperphosphorylated Tau synergistically drive neuronal necroptosis

This study shows that glucose hypometabolism and hyperphosphorylated Tau work together to cause neuronal death through necroptosis in a mouse model.

Repurposed COMT Inhibitors Tolcapone and Entacapone Selectively Suppress Aggregation and Seeding of P301 Mutant TAU in Human Neuronal Models

NMNAT2-SARM1 Axis Drives Redox Failure and Disrupts APP Processing in Neurons

This study shows that NMNAT2 loss disrupts APP processing in neurons by causing redox failure and proteostasis disruption, with SARM1 playing a key role in this process.

Seeding patient-derived tau induces tauopathy-specific aggregation and lysosomal disruption in human cells

This study uses patient-derived tau aggregates to induce disease-specific tauopathy features in human cells, revealing distinct pathological responses across tau strains.

The exocyst is an insulin-sensitive regulator of amyloid precursor protein trafficking and amyloid-beta generation in neurons

The paper shows the exocyst regulates APP trafficking and amyloid-beta generation in neurons, with insulin signaling shifting exocyst activity away from APP to GLUT4.

HIV and Cocaine exposure promote Tau phosphorylation through RSK-1 in a GSK3β-independent manner.

This study identifies RSK1 as a central mediator of Tau phosphorylation in response to HIV and cocaine exposure, revealing a GSK3β-independent mechanism.

Humanized Klotho haplotypes cause widespread transcriptomic changes in mouse brain

This study shows that human KL haplotypes FC and VS cause widespread transcriptomic changes in mouse brains at 12 months old, affecting mitochondrial, ribosomal, and synaptic functions, and linking them to Alzheimer's Disease pathogenesis.

The Alzheimer's disease neurodegenerative cascade reconstructed in human L2/3 excitatory neurons

The paper reconstructs the Alzheimer's disease neurodegenerative cascade in human L2/3 excitatory neurons using single-nucleus RNA sequencing data from multiple datasets.

A metabolite extracted from E. coli suppresses tau aggregation

This study identifies a metabolite from E. coli that suppresses tau aggregation in vitro and in live bacteria, suggesting its potential for modulating tauopathies.

RUNX1 and YY1 modulate neuronal fate and energy metabolism in Alzheimer's disease

This study identifies RUNX1 and YY1 as master transcription factors modulating neuronal fate and energy metabolism in Alzheimer's disease using patient-derived induced neurons and post-mortem brain data.

Chronic potentiation of metabotropic glutamate receptor 2 with a nanobody accelerates amyloidogenesis in Alzheimer's disease.

This study shows that chronic activation of mGlu2 receptors with a nanobody accelerates amyloid formation and worsens memory deficits in Alzheimer's disease models.

Discovery and Preclinical Validation of a Clinically Optimized Mitochondrial Complex I Modulator for Alzheimer's Disease

This paper describes the discovery and validation of C273, a mitochondrial complex I modulator that reduces Alzheimer's disease pathology by enhancing cellular resilience through AMPK-mediated pathways.

Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer's and wild-type mice

This study shows lactate treatment improves cognitive function and molecular biomarkers in Alzheimer's mice and wild-type controls.