Alzheimer's disease research and treatments

This study identifies initial cleavage sites of γ-secretase substrates NRG1 and CDH1 and confirms the phenylalanine rule at the P2 position.

This study identifies neuronal lysosomal acid lipase (LAL) loss as a driver of amyloid pathology in Alzheimer's disease by linking disrupted lipophagy to Aβ accumulation and cognitive deficits.

This study examines the interactions between A{beta}, tau, LATE-NC, -synuclein, and APOE {varepsilon}4 in 480 post-mortem brains, finding that tau is the strongest predictor of neurodegeneration while LATE-NC primarily affects hippocampal neuron loss.

The paper identifies miR-7a-Klf4 as a regulator of neuroinflammation and ferroptosis in Alzheimer's disease and shows its therapeutic potential.

The paper identifies transcriptional changes in interneurons across Alzheimer's disease stages in mice, revealing disease progression markers and potential therapeutic targets.

This paper designs an orally bioavailable small molecule that targets RNA to reduce 4R tau protein abundance and alleviate disease phenotypes in a mouse model.

This study shows that FGFR1 agonists like FGF1 and FGL improve cognitive function and reduce pathology in an Alzheimer's disease mouse model.

This study shows that PSEN1 mutations disrupt regulated intramembrane proteolysis in astrocytes, leading to enhanced inflammatory responses and contributing to familial Alzheimer's disease progression.

This study shows that pathological tau spreads from the olfactory epithelium to brain regions in AD models and suggests targeting the olfactory epithelium to slow tauopathy progression.

This study uses scRNA-seq and network analysis to identify cell-type-specific transcriptional changes in Alzheimer's disease, revealing dysregulation in neurons and key roles of vascular cells.

This study shows that overexpressing APPL1 in neurons causes AD-like endosomal and synaptic dysfunction, cholinergic neurodegeneration, and memory deficits in mice.

The paper uses genetic perturbation and machine learning to analyze the energetics of amyloid beta nucleation, revealing its genetic architecture and transition state structure.

This study uses molecular dynamics simulations to analyze how phosphorylations of tau-R2 affect its binding to tubulin and the stability of the tau-microtubule interface.

This study shows that reducing SIRT2 in microglia worsens cognitive decline and amyloid pathology in Alzheimer's disease models.

This study shows that Ydj1, a heat shock protein 40, prevents amyloid fibril formation by promoting heterotypic phase separation of tau through electrostatic and hydrophobic interactions.

This study shows that extracellular tau's synaptotoxic effects are mediated by its microtubule-binding region, and targeting this region can reverse synaptic plasticity disruption.

This paper shows lecanemab binds to amyloid-β fibrils from Alzheimer's disease mouse models with flexible N-termini, including type-I, type-II, and Arctic folds, but not those with fixed N-termini like in tg-SwDI mice.

The paper examines iron levels and lipid peroxidation in DSAD brains, finding increased iron and lipid damage compared to AD and controls, suggesting ferroptosis involvement.

The paper demonstrates that CARs based on AD antibodies can detect and discriminate between tau and distinct Aβ species, suggesting their potential for targeted AD therapies.

This study investigates how Aβ dimers alter fast and localized calcium elevations in astrocytes, finding increased frequency and occupancy of calcium events mediated by P2Y1 receptors and ER Ca2+ release.

The paper reports cryo-EM structures of tau filaments from individuals with P301L and P301T MAPT mutations, revealing distinct filament folds associated with FTDP-17.

This study shows isoliquiritigenin improves cognitive function and reduces tau phosphorylation, oxidative stress, and mitochondrial dysfunction in a mouse model of Alzheimer's disease.

This study identifies milk lactalbumin-derived peptides that disrupt tau aggregation in Alzheimer's disease by altering PHF core structure and blocking subunit addition.

This paper identifies an APP-selective BACE1 inhibitor, FAH65, which shows substrate and enzyme selectivity, reduces Aβ levels, and improves cognitive performance in an AD mouse model.

This study integrates multi-omics data from Drosophila and human Alzheimer's disease models to identify pathways involved in neurodegeneration.

The paper compares proteome and transcriptome changes in DSAD brains to AD and healthy controls, finding elevated APOE in specific cell types.

The paper investigates early hyperexcitability in mossy cells of the dentate gyrus in the Tg2576 Alzheimer's model, finding increased excitatory events and intrinsic changes before memory deficits occur.

This study uses molecular simulations to analyze Abeta42 monomer diffusion on fibril surfaces, finding orientation and surface roughness significantly affect diffusion and aggregation.

This study shows that astrocytic K+ clearance is reduced in the hippocampus of symptomatic 5xFAD mice, correlating with decreased Kir4.1 channel expression and altered neuronal signaling.