Alzheimer's disease research and treatments

Amyloidogenic proteolysis of APP regulates glutamatergic presynaptic function

The paper shows that APP-CTFβ regulates glutamatergic synaptic transmission and that Aβ counteracts its hyperexcitability effects in Alzheimer's disease.

MAPT regulates autophagic-lysosomal function and phagocytosis in human microglia

This study shows that pathogenic MAPT mutations impair microglial lysosomal and autophagic functions, affecting tau clearance and degradative capacity.

The Alzheimer's disease risk gene SORL1 is a regulator of excitatory neuronal function

This study shows that SORL1 deficiency in neurons alters synaptic protein interactions, causes hyperexcitability, and impairs synaptic plasticity, linking endosomal recycling defects to Alzheimer's disease pathogenesis.

Inhomogeneous Tau polymerization, core-shell organization, and seed formation during Tau condensate aging

This study shows how Tau condensates age into elastic networks with inhomogeneous polymerization and seed formation, providing mechanistic insight into their transition to pathological aggregates.

Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimers disease

Tau Disaggregation by a CNS-Permeable Small Molecule Reduces Fibril and Oligomer Burden and Preserves Proteostasis and Behavior

This paper develops a small molecule that disaggregates tau fibrils and oligomers, reduces pathology, and preserves function in a tauopathy mouse model.

Sequential Molecular Interactions Shape Aβ42 Aggregation, Propagation, and Toxicity

The paper investigates how sequential molecular interactions modulate Aβ42 aggregation properties and toxicity across successive cycles, showing that early interactions with exogenous peptides alter aggregate characteristics and propagation.

Repositioning of polyubiquitin alters the pathologic tau filament structure

This study shows that polyubiquitin repositioning affects tau filament structure in tauopathies, altering their seeding activity in mice.

Hyperactivation of the AXL-ICD/SIRT2 axis by Amyloid-β impairs astrocytic autophagic flux and exacerbates neuroinflammation

This study identifies the AXL-ICD/SIRT2 axis as a mechanism by which amyloid-β impairs astrocytic autophagy and exacerbates neuroinflammation in Alzheimer's disease.

Amyloid Polymorphism of Lysozyme Governs Cross-Seeding of Insulin Aggregation

This study shows that different polymorphs of lysozyme influence the structure and toxicity of cross-seeded insulin fibrils.

Geometric characterization of the HSV - 1 glycoprotein B - amyloid β interaction in Alzheimer's disease using Forman-Ricci curvature

The paper uses Forman-Ricci curvature to analyze residue interaction networks in HSV-1 gB-Aβ complexes, revealing geometric changes not captured by conventional methods.

A mathematical model of pathology progression in the TgF344-AD rat model of Alzheimer's disease

The paper develops a mathematical model to simulate pathology progression in the TgF344-AD rat model of Alzheimer's disease, linking amyloid-β accumulation to neuronal loss and cognitive decline.

MTHFR*677C>T produces distinct prodromal disease signatures in a mouse model of late-onset Alzheimer's disease

The paper shows that the MTHFR*677C>T variant in a mouse model of LOAD produces distinct transcriptional and proteomic signatures related to cerebrovascular and synaptic biology.

Gangliosides GM3 And GD3 Modulate Insulin Aggregation Pathways and Reduce Cytotoxicity Through Structural Remodeling

This study shows gangliosides GM3 and GD3 accelerate insulin aggregation into non-fibrillar structures that are less toxic than fibrillar aggregates, suggesting potential therapeutic implications for Type-2 Diabetes.

CSF complement proteins are associated with early tau pathology and synaptic damage in an asymptomatic population at risk of Alzheimer's disease

The paper investigates the association between CSF complement proteins and early AD pathology in at-risk individuals, finding C1q and Factor H linked to tau and synaptic markers.

A conserved serotonin receptor pathway is a druggable modifier of Tau pathology, neural circuit formation and neurodegeneration

This study identifies a druggable serotonin receptor pathway that modifies Tau pathology and neural circuit formation in a Drosophila model of tauopathy.

SorCS1 promotes synaptic and cognitive resilience despite amyloid pathology in Alzheimer's disease model mice

This study shows that SorCS1 overexpression in Alzheimer's disease model mice preserves cognitive function and synaptic integrity without reducing amyloid levels.

Imipramine binds to Amyloid-beta(1-42) monomers in vitro, as shown by NMR spectroscopy.

The paper shows imipramine binds to A{beta}(1-42) monomers in vitro using NMR spectroscopy, but not to A{beta}(1-40).

Restoring neurovascular coupling in Alzheimer's disease tauopathy through M1 mAChR modulation

This study shows that activating M1 mAChR with VU0486846 restores neurovascular coupling deficits in tauopathy mice, with sex-specific effects.

Mapping Alzheimer's neuropathology signatures to the whole brain transcriptome using machine learning data fusion

Cell type-specific logistic regression estimators trained on 427 ROSMAP prefrontal donors project Braak- and β-amyloid-like transcriptomic signatures onto the 108-region Siletti atlas, flagging brainstem, hypothalamic and rostral hippocampal regions.

Ahead of the membrane curve: in silico insights into amyloid-β aggregation

This study uses molecular dynamics simulations to show that membrane curvature influences Aβ42 aggregation by altering peptide-lipid interactions and conformational dynamics.

Mechanochemically Programmed, Oligomer-Selective Amyloid Assembly via Axial Rotation

This study shows that axial rotation can control amyloid assembly pathways, producing oligomer-rich structures without chemical additives.

Loss of neuronal population organization links pathology to behavior in a model of Alzheimer's disease

This study links neuronal population organization disruption to behavioral changes in a macaque model of early-stage Alzheimer's disease and related dementias.

Cross-Regional Trajectory Analysis Reveals Distinct Temporal Progression of Shared Proteomic Programs in Alzheimer's Disease

The paper analyzes proteomic trajectories in Alzheimer's disease to show distinct temporal progression of shared molecular programs across brain regions.

Syndecan-4 exerts canonical heparan sulfate-dependent and noncanonical heparan sulfate-independent functions that regulate Aβ amyloid homeostasis

This study shows that Syndecan-4 has both HS-dependent and HS-independent effects on Aβ amyloid homeostasis, reducing amyloid deposition in a mouse model.

Beyond Co-Existence: Early α-Synuclein-Amyloid-β42 Association from Molecular Dynamics Simulations

This study uses molecular dynamics simulations to show that early α-synuclein association with Aβ42 oligomers depends on their initial configuration, with distinct interaction patterns observed based on Aβ42's oligomeric state.

Swedish APP follows distinct neuronal traffickingitineraries that underlie its increased Aβ-cleavage

This study shows that Swedish APP (APPSwe) follows distinct neuronal trafficking routes compared to wild-type APP, leading to increased Aβ production.

Pseudotime analysis of 2,106 brains across nine regions reveals conserved immune, neuronal, and myelin regulatory programs in Alzheimer's disease

The paper uses pseudotime analysis on bulk RNA-seq data from Alzheimer's disease brains to identify conserved and region-specific molecular programs across nine brain regions.

TRAPPC8 Is an Endogenous Brake on UFMylation That Suppresses Tauopathy

This study identifies TRAPPC8 as a brake on UFMylation that suppresses tauopathy by interacting with UBA5, showing its therapeutic potential in Alzheimer's disease.

Loss of calbindin and rise in pT217-tau in aging monkey prefrontal cortical dendrites

The paper shows that aging macaques lose calbindin and gain pT217-tau in prefrontal cortical dendrites, linking calbindin loss to increased tau pathology and AD risk.