Alzheimer's disease research and treatments

Distinct Filament Conformation for Receptor-Bound Amyloid-β from Alzheimers Disease Brain

The paper identifies a distinct receptor-bound amyloid-β filament conformation in Alzheimer's disease brain that interacts with prion protein and causes synaptic damage.

APOE4 disrupts the central dogma by arresting neuronal proteome dynamics

This study shows APOE4 disrupts neuronal proteome dynamics by impairing proteostasis, leading to protein accumulation and cellular stress before Alzheimer's disease onset.

Deciphering the mechanism of protein aggregation and effects of inhibitors using single-molecule mass photometry

This study uses single-molecule mass photometry to directly observe protein aggregation kinetics and identify inhibitor effects on aggregation mechanisms.

Neural Network-Enhanced Investigation of Ferroptosis and Druggability in Early-Onset Alzheimers Disease

This study identifies ferroptosis-related biomarkers in early-onset Alzheimer's disease using machine learning and develops a diagnostic model with high AUC-ROC values.

Patient-Derived PSEN1 Cerebral Organoids Revealed Parallel Development of Amyloid-β Accumulation and Network Dysfunction

This study uses patient-derived cerebral organoids to show that amyloid-β dysregulation correlates with network hyperexcitability in early Alzheimer's disease.

Long-term Locus Coeruleus Stimulation Exacerbates Tau Pathology in PS19 Mice

This study shows that long-term locus coeruleus stimulation worsens memory, synaptic plasticity, and Tau pathology in PS19 mice.

Immunoproteasome Deficiency Impairs Microglial Clearance and Worsens Tau and Amyloid Pathology

This study shows that immunoproteasome deficiency in mice worsens tau and amyloid pathology by impairing microglial clearance.

Distribution of big tau isoforms in the human central and peripheral nervous system

The paper characterizes big tau isoforms in human nervous system tissues and CSF, finding they are enriched in the peripheral nervous system and largely unaffected by neurodegenerative disease.

Small-molecule-induced species redistribution drives amyloid remodeling along a conserved kinetic landscape

The paper shows small molecules remodel amyloid networks by redistributing protein populations along a conserved kinetic landscape, influenced by concentration, self-association, and environmental factors.

A validated neuronal SH-SY5Y platform reveals critical experimental variables for reproducible Aβ 1-42 self-assembly neurotoxicity assessment

The paper establishes a neuronal SH-SY5Y model to assess Aβ1-42 self-assembly neurotoxicity, showing that toxicity depends on aggregation state, cell differentiation, and assay type.

Multivalent Tau-Fyn interactions cooperatively arrest postsynaptic density condensate dynamics

This study investigates how Tau and Fyn interact to regulate postsynaptic density condensate dynamics, showing that their multivalent interactions cooperatively arrest condensate components.

Predicting Biological Age Using an Accumulated Neurotoxicity Biomarker for Amyloid Beta Oligomers

This paper develops a model linking accumulated neurotoxicity from amyloid beta oligomers to biological age, showing that increasing half-lives of Aβ monomers and oligomers accelerates aging.

Molecular Dynamic simulations of Aβ42 dimers with solid-state NMR restraints capture the key structural motifs in Aβ42 fibrillation pathways

This study uses molecular dynamics simulations with solid-state NMR restraints to analyze Aβ42 dimer structural changes during fibrillation, revealing key motifs and pathway differences with and without membrane interactions.

Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: Implications for translational validity to the human

The paper analyzes brain volume changes in humanized APOE mice across age and genotype, finding age-related increases in total brain volume and no significant sex or genotype differences in localized volume changes.

Divergent transcriptomic transition programs in Alzheimer disease: immune priming and synaptic collapse in females versus organelle membrane bifurcation in males

The paper identifies divergent transcriptomic transition programs in Alzheimer's disease between females and males, showing distinct molecular pathways in disease progression.

Structural presentation of amyloid β by HLA

The paper presents the first experimental structure of an Alzheimer's Aβ peptide bound to an HLA molecule, revealing key interactions and polymorphic binding sites.

Shared lipidome and proteome signatures of frontotemporal lobar degeneration and Alzheimer's disease

The paper identifies shared lipid and proteomic alterations in frontotemporal lobar degeneration and Alzheimer's disease, with greater changes in FTLD frontal cortex.

APOE4 genotype and old age interact to impact cerebrovascular function, brain volume, and neuroinflammation in mice

This study investigates how APOE4 genotype and old age interact to affect cerebrovascular function, brain volume, and neuroinflammation in mice, finding that the interaction impacts these outcomes while age alone affects cognitive function and arterial stiffness.

Galectin-3 drives tau-associated neuroinflammation, white matter degeneration and proteomic dysregulation

This study shows that Galectin-3 promotes tau pathology, neuroinflammation, white matter degeneration, and proteomic dysregulation, and that its deletion reduces these effects.

tRNA-derived fragments elevated in Alzheimer's disease facilitate Tau aggregation

This study identifies tRNA-derived fragments (tRFs) as key regulators of Tau aggregation in Alzheimer's disease and shows their potential as therapeutic targets.

Patient-derived tau-seeded human neuronal chimeras recapitulate mature Alzheimer's tau pathology and uncover human-specific neuronal vulnerability

This study develops a human neuronal chimera model to study Alzheimer's tau pathology, showing human-specific vulnerability and recapitulating mature AD features in vivo.

Local translation controls early reactive changes in perisynaptic astrocyte processes at pre-symptomatic stages of Alzheimers disease

The paper identifies astrocyte perisynaptic processes as sites of early translational dysregulation in Alzheimer's disease, linking it to synaptic dysfunction and disease initiation.

Disrupted myelin homeostasis in grey matter of Alzheimer's disease

This study identifies specific myelin disruption in cortical grey matter of Alzheimer's disease, linked to tau pathology and impaired oligodendrocyte differentiation.

A Comparative Study of Plasma Biomarkers of Neurodegeneration in Rhesus Monkeys (Macaca mulatta) and Baboons (Papio anubis)

This study compares age-related changes in plasma neurodegeneration biomarkers between rhesus monkeys and baboons using a multiplex assay, finding species-specific patterns and associations with brain atrophy.

The Pick fold in tau filaments from human MAPT mutants

This study reports cryo-EM structures of tau filaments from MAPT mutants, showing how specific mutations alter the Pick fold structure and enable reconstitution of variants.

Context-dependent toxicity of human Tau isoforms in a Drosophila tauopathy model

This study shows that human Tau isoforms have context-dependent toxicity in a Drosophila model, with variations in expression timing, tissue type, and neuronal identity affecting degeneration outcomes.

CTE-Type Tau Filaments in Alzheimer's Disease with Co-morbid LATE-NC

The paper determines the structure of tau filaments in Alzheimer's disease patients with co-morbid LATE-NC using cryo-electron microscopy, revealing a CTE-type tau fold in addition to the Alzheimer's fold.

Trisomy 21 cerebral organoids exhibit Alzheimer's disease amyloid and apolipoprotein E co-pathologies

This study shows that trisomy 21 cerebral organoids exhibit Alzheimer's disease amyloid and apoE co-pathologies, with apoE playing a key role in the disease process.

Elevation of the mechanically-sensitive protein emerin links nuclear mechanotransduction to tau-induced cytoskeletal remodeling in neurons

This study identifies emerin as a mediator of cytoskeletal remodeling in tauopathy by showing its elevation and relocalization in neuronal models of tauopathy, linking nuclear mechanotransduction to neurotoxicity.

Targeted proteomics of postmortem human brain reveals neurobiologic heterogeneity in Alzheimer's disease using NULISA technology

This study uses targeted proteomics to identify protein expression differences in Alzheimer's disease cases with varying clinical and neuropathological features.