Alzheimer's disease research and treatments

The monomeric conformational ensembles of Aβ40 and Aβ42 encode their differential amyloid aggregation propensity

Chronic central-targeted Interleukin-6 overexpression promotes hippocampal and cortical neuropathology in the Tg2576 mouse model of Alzheimer's disease

This study shows that chronic central IL-6 overexpression in Tg2576 mice worsens amyloidosis-related neuropathology and alters cortical and hippocampal gene expression, with sex-dependent effects.

Aβ Aggregates Bind the U1 Spliceosomal Ribonucleoprotein in Alzheimer Disease Brain

The paper identifies that Aβ aggregates bind the U1 snRNP in Alzheimer's disease brain, linking Aβ aggregation to spliceosome dysfunction and connecting it to other fibril-forming proteins in neurodegenerative diseases.

A mitochondrial-immune axis drives the transcriptomic transition from brain aging to Alzheimer's disease

This study identifies a sex-modulated mitochondrial-immune axis linking brain aging to Alzheimer's disease through integrative transcriptomic analyses across multiple datasets.

GWAS on short tandem repeats identifies novel genetic mechanisms in Alzheimer's disease

This study conducts GWAS on short tandem repeats (STRs) to identify novel genetic mechanisms in Alzheimer's disease using data from ~330,000 individuals.

Lipidated ApoE is found in nanoscale proximity to Aβ aggregates in human Alzheimer brains.

The paper shows lipidated ApoE is closely located to Aβ aggregates in human Alzheimer's brains, suggesting a role in plaque formation.

Integration of transcriptional signatures from brain tissue and plasma extracellular vesicles of a preclinical tauopathy mouse model

The paper integrates transcriptomic data from brain tissue and plasma extracellular vesicles in a tauopathy mouse model, identifying shared non-coding RNA signatures that reflect central nervous system changes.

Tau aggregate replication occurs at the pre-synapse of cultured human neurons and increases with application of TNFa

The paper shows TNFα promotes tau aggregation at pre-synapses in human neurons, forming non-fibrillar aggregates that replicate rapidly.

Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer knock-in mouse phenotypes

This study shows that a high-fat, high-sugar diet worsens cognitive deficits in Alzheimer's mouse models through metabolic stress in specific brain cells, independent of amyloid or tau pathology.

Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice

This study shows neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD mice by lowering BACE1 and other proteins in these structures.

AETA peptide contributes to Alzheimer's disease signature of synapse dysfunction.

This study identifies AETA peptide as a novel contributor to synaptic dysfunction in Alzheimer's disease, particularly in females, through post-mortem analysis and a mouse model.

APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation

This study shows that APOE4 accelerates menopause-related metabolic decline and impairs bioenergetic adaptation in the brain, increasing Alzheimer's disease risk.

Differential vulnerability of CA1 pyramidal neuron cell types in the 5xFAD Alzheimer's disease mouse model

The paper examines how different CA1 pyramidal neuron cell types in the 5xFAD Alzheimer's mouse model show varying vulnerability to amyloid pathology across disease progression.

Endogenously generated Dutch-type Aβ nonfibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation

This study shows that nonfibrillar Aβ aggregates in APPE693Q mice disrupt presynaptic function without causing inflammation.

Mitochondrial NADK2-dependent NADPH controls Tau oligomer uptake in human neurons

The paper shows that mitochondrial NADK2-dependent NADPH synthesis mediates Tau oligomer uptake in neurons via LRP1, creating a cycle that exacerbates TauO toxicity.

Mapping cross-domain drivers of Alzheimer's disease risk through integrated network analysis

The paper identifies cross-domain drivers of Alzheimer's disease risk by integrating network analysis across biological domains.

Network-Level Characterization of Spontaneous Calcium Activity in an In-Vitro Alzheimer's Disease Model

This study compares network-level calcium dynamics in two in vitro Alzheimer's disease models, finding differences in hyperactivity and cell cooperation between familial AD and an accelerated model.

A Toxic Tau-PFKFB3 Circuit Reduces F2,6BP Levels and Drives Neurodegeneration

This paper identifies the PFKFB3-F2,6BP metabolic axis as a key driver of Alzheimer's disease by linking metabolic dysregulation to genomic stability and Tau proteostasis, showing that F2,6BP supplementation rescues AD phenotypes across multiple models.

Proteomic analysis of human leptomeningeal matrisome identifies changes in Alzheimer's disease

The paper performs proteomic analysis of human leptomeningeal matrisome in Alzheimer's disease and controls, identifying disease-associated changes in ECM proteins and signaling pathways.

Alzheimer's disease associations with increased Biondi body amyloid in hippocampal-associated choroid plexus epithelial cells and ependymal cells

The paper investigates the association between Alzheimer's disease and Biondi body amyloid in hippocampal-associated choroid plexus epithelial cells and ependymal cells, finding a near-significant increase in BB-containing CPECs and a significant increase in BB-like amyloid in ependymal cells in AD.

Reduced SH3RF3 may protect against Alzheimer's disease by lowering microglial pro-inflammatory responses via modulation of JNK and NFkB signaling

The paper identifies protective SH3RF3 variants that delay Alzheimer's onset by reducing microglial inflammation through JNK and NFkB pathway modulation in PSEN1G206A carriers.

O-GlcNAcylation effect on Tau in modulating its seeding and cellular transmission in Alzheimer's Disease

This study investigates how O-GlcNAcylation affects Tau aggregation and toxicity in Alzheimer's Disease, showing reduced seeding and toxicity in O-GlcNAcylated Tau.

Curated neurodegeneration axis signals are sensitive to cell composition and analytic choices: an adversarial re-analysis of a transcriptomic scoring pipeline

The paper re-analyzes a transcriptomic scoring pipeline for neurodegeneration axes, finding results sensitive to cell composition and analytic choices, and provides code for improved validation.

From APOE Genetics to AI-Designed Drug Candidates: An Integrated Pipeline for Oral, Brain-Penetrant ACAT1 Inhibitors in Alzheimer's Disease

This paper presents an AI-driven drug discovery platform for designing oral, brain-penetrant ACAT1 inhibitors for Alzheimer's disease, identifying promising lead candidates with favorable properties.

Inhibition of NF-κB signaling pathway in astrocytes facilitates amyloid-β clearance by kallikrein-related peptidase 7

This study shows that inhibiting the NF-κB signaling pathway in astrocytes increases KLK7 expression and enhances amyloid-β clearance, suggesting a therapeutic target for Alzheimer's disease.

Heterotypic FG-Nup98-tau condensates form nested assemblies through stoichiometry-dependent phase transitions

This study investigates how FG-Nup98 and tau form heterotypic condensates through phase transitions, revealing their potential role in disrupting nuclear pore permeability.

Integration of Alzheimer's GWAS, 3D genomics, and single-cell CRISPRi non-coding screen implicates causal variants in a microglial enhancer regulating TSPAN14.

Effects of PTMs on Tau Protein Aggregation: Insights from HCG and Atomistic MD Simulations

The paper evaluates how specific PTMs affect tau protein aggregation using HCG and atomistic MD simulations, showing their impact on structural properties and aggregation behavior.

Alzheimer's disease-associated Presenilin 2 N141I mutation impairs neuronal lipid homeostasis and mitochondrial dynamics through selective downregulation of the Golgi exchange factor Gbf1

This study shows that the N141I PS2 mutation disrupts lipid homeostasis and mitochondrial dynamics by downregulating Gbf1, suggesting a new amyloid-independent pathway in Alzheimer's disease.

Genetic ablation of neuronal mitochondrial calcium uptake halts Alzheimer's disease progression

This study shows that reducing neuronal mitochondrial calcium uptake in AD mouse models decreases pathology, synaptic dysfunction, and cognitive decline.