Alzheimer's disease research and treatments

APP and β-amyloid modulate protein aggregation and dissociation from recycling endosomal and exosomal membranes

The paper shows APP and Aβ-peptides modulate protein aggregation and DCG biogenesis in Drosophila cells, with mutant Aβ-peptides disrupting these processes and causing AD-like pathologies.

Atomic structures of medin and Aβ fibrils reveal polymorphic remodeling in mixed amyloid systems

This study determines the cryo-EM structures of Aβ40 and medin fibrils in vitro, revealing polymorphic remodeling and mixed amyloid interactions.

Uncovering Plaque-Glia Niches in Human Alzheimer's Disease Brains Using Spatial Transcriptomics

The paper uses spatial transcriptomics to analyze Aβ plaques and glial interactions in AD brains, finding that low Aβ areas show more neuronal loss and high-glia areas show inflammation and neurodegeneration.

Interpretable deep learning framework for understanding molecular changes in human brains with Alzheimer's disease: implication for microglia activation and sex differences

This paper uses an interpretable deep learning framework to analyze transcriptomic data from Alzheimer's disease brain tissues, identifying gene signatures and sex-specific modules associated with microglia activation and neuronal loss.

Genetic insights into the association between inflammatory bowel disease and Alzheimer's disease

This study investigates the genetic overlap between inflammatory bowel disease and Alzheimer's disease, finding distinct myeloid cell-specific risk factors and some protective associations.

A genetically encoded selection for amyloid-β oligomer binders

This paper develops a genetically encoded biosensor to detect and select amyloid-β oligomer binders, identifying new binders more effective than existing ones at delaying secondary nucleation.

Lipid Mediated Formation of Antiparallel Aggregates in Cerebral Amyloid Angiopathy

This study investigates the structural characteristics of amyloid-beta aggregates in cerebral amyloid angiopathy, identifying antiparallel beta-sheet structures linked to lipid-mediated aggregation.

Amyloid-beta fibrils induce calcium phosphate crystallization via catalysis of ATP hydrolysis

This study shows that amyloid-beta fibrils catalyze ATP hydrolysis, leading to calcium phosphate crystallization, which may explain calcification in Alzheimer's disease.

Anionic lipid catalyzes the generation of cytotoxic insulin oligomers

This study shows that anionic lipids like DMPG influence insulin aggregation pathways and intermediate formation, with soluble intermediates being more cytotoxic than fibrils.

Amyloid beta aggregation promoted by iron leads to neuronal loss in an ex vivo model of Alzheimer's disease

This study shows that iron promotes Aβ fibrillization and synergizes with Aβ to cause neuronal death in an ex vivo AD model.

Cell type-specific master metabolic regulators of Alzheimer's disease

The paper identifies cell-type-specific metabolic regulators in Alzheimer's disease using scFUMES, revealing key interactions that reduce pathological tau species.

Self-consistent analytical solutions to the kinetics of lipid-induced protein aggregation

This study develops an analytical model to describe lipid-induced protein aggregation kinetics, capturing both one-step and two-step nucleation mechanisms and predicting key kinetic observables.

Increased cerebrospinal fluid and plasma apoE glycosylation is associated with reduced levels of Alzheimer's disease biomarkers

The paper examines apoE glycosylation in CSF and plasma samples from ADNI, finding reduced glycosylation in MCI and progressors, and associations with AD biomarkers like t-tau, p-tau181, and Aβ1-42.

The selective amyloid-driven failure of cholinergic medial septal neurons in aging mice perturbs REM sleep, cognition and emotion, and broadcasts amyloid to other brain regions

This study shows that amyloid accumulation in medial septal cholinergic neurons of aging mice leads to REM sleep loss, cognitive and emotional deficits, and amyloid spread to other brain regions.

AAV-based temporal APOE4-to-APOE2 replacement reveals rebound adaptation and RAB24-mediated Aβ and cholesterol dysregulation

This study uses AAV-based gene therapy to replace APOE4 with APOE2 in mice, revealing that long-term replacement reverses AD pathology while short-term replacement worsens it, with RAB24 playing a key role.

Direct binding of TDP-43 and Tau drives their co-condensation, but suppresses Tau fibril formation and seeding

This study shows that TDP-43 and Tau directly interact, promoting co-condensation but reducing Tau fibril formation and seeding.

Metabolites associated with type 2 diabetes and Alzheimer's disease trigger differential intracellular signaling responses in mouse primary neurons

The paper investigates how metabolites linked to type 2 diabetes and Alzheimer's disease affect intracellular signaling in mouse neurons, identifying specific pathway activations associated with disease progression or protection.

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models

The paper uses snRNA-seq in Drosophila to study how AD-associated proteins affect peripheral tissues, finding distinct impacts of Aβ42 and Tau on sensory neurons and non-neuronal tissues.

MiRNA-501-3p and MiRNA-502-3p: A Promising Biomarker Panel for Alzheimer's Disease

This study identifies miR-501-3p and miR-502-3p as potential biomarkers for Alzheimer's disease by showing their upregulation in AD-related samples.

Impaired hippocampal circuit function underlying memory encoding and consolidation precede robust Aβ deposition in a mouse model of Alzheimer's disease

The paper identifies impaired hippocampal circuit function in a mouse model of Alzheimer's disease before Aβ deposition, highlighting issues in theta-gamma oscillations and place cell reactivation during sleep.

γ-Secretase-mediated endoproteolysis of neuregulin-1 and E-cadherin

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

Age-dependent remodeling of the sciatic proteome in 5xFAD mice can be attenuated by exercise or donepezil treatment to maintain neuromuscular function

This study shows that exercise or donepezil treatment can reduce proteomic changes in sciatic nerves of 5xFAD mice, preserving neuromuscular function before cognitive decline.

An Early Olfactory Transcriptomic Signature of Tauopathy: Gbp2b Emerges as a Candidate Biomarker of Tau-Driven Neuroinflammation

The paper identifies Gbp2b as an early biomarker of tauopathy in the olfactory epithelium of PS19 mice through transcriptomic analysis across different ages.

Loss of neuronal lysosomal acid lipase drives amyloid pathology in Alzheimer's disease

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.

Alzheimer's disease and its co-pathologies: implications for hippocampal degeneration, cognitive decline, and the role of APOE ϵ4

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.

Long-term antiplatelet therapy protects against cerebral but not parenchymal amyloid plaque formation and neurodegeneration in transgenic mice of Alzheimers disease

This study shows that long-term antiplatelet therapy with clopidogrel reduces cerebral amyloid angiopathy and soluble Aβ42 levels but not parenchymal amyloid plaques or neurodegeneration in APP23 mice.

Single-Domain Antibody-Based Autophagosome-Targeting Chimera for Tau Clearance and Motor Function Restoration in Tauopathies

This paper presents a single-domain antibody-based protein degrader that reduces tau levels and improves motor function in tauopathy models.

MiR-7a-Klf4 axis as a regulator and therapeutic target of neuroinflammation and ferroptosis in Alzheimer's disease

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

Amyloid pathology compresses dynamic range and degrades spatial coding in an Alzheimer's mouse model

This study shows that amyloid pathology reduces neuronal dynamic range and impairs spatial coding in an Alzheimer's mouse model.

SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain

This study shows that increasing SORLA levels in aged tauopathy mice reduces multiple pathological effects, including tau phosphorylation, inflammation, and synaptic dysfunction.