Alzheimer's disease research and treatments

β-motifs and molecular flux promote amyloid nucleation at condensate interfaces

This study introduces FD-MD simulations to show that condensate interfaces enhance amyloid nucleation through β-motifs and molecular flux, leading to different growth morphologies and aging trajectories.

Divergent consequences of PSEN1 knockout and PSEN2 knockout in stem cell derived models of the brain

This study compares the effects of PSEN1 and PSEN2 knockout in iPSC-derived brain cells, finding distinct impacts on endo-lysosomal systems and APP cleavage.

APOE4 Allele Frequencies Show Dramatic Variation Across Indian Populations

The paper examines APOE ε4 allele frequencies across 9,524 individuals from 83 Indian populations, revealing significant variation and associations with lipid phenotypes.

Adolescent Social Isolation Facilitates Tau Spread in Raphe Nuclei Linking Depression and Hyperalgesia in Alzheimers Disease

This study shows that adolescent social isolation promotes tau spread in raphe nuclei, causing depression-like and pain-related symptoms in Alzheimer's disease.

Stage-dependent tau post-translational modifications map the spatiotemporal progression of Alzheimer's disease

This study maps stage-dependent tau post-translational modifications across Alzheimer's disease progression, revealing early phosphorylation and later ubiquitination events associated with tau aggregation.

BET protein inhibitor JQ1 reduces inflammation and hippocampal amyloid-β level without altering Tau phosphorylation in LPS-challenged adult wild-type mice

This study shows that JQ1, a BET inhibitor, reduces inflammation and hippocampal amyloid-β levels but not Tau phosphorylation in LPS-challenged mice.

Structural hormesis in protein aggregation: A minimal mechanistic model

The paper develops a minimal mechanistic model showing that protein aggregation can exhibit hormesis, with low-dose stimulation and high-dose inhibition, arising from network topology.

Repetitive induction of a hibernation-like brain state slows amyloid pathology

The paper shows that inducing a hibernation-like brain state in AD mice slows amyloid plaque accumulation and reduces neuroinflammation without targeting specific pathways.

Acute exposure of mouse and human hippocampal slices to tau oligomers reversibly impairs sharp-wave ripples

The paper investigates the effects of tau oligomers on sharp-wave ripples in mouse and human hippocampal slices, finding reversible impairments in SWR parameters depending on species and tau preparation.

Methylomic signatures of tau and amyloid-beta in transgenic mouse models of Alzheimer's disease neuropathology

The paper identifies DNA methylation changes in transgenic mouse models of Alzheimer's disease, showing distinct patterns for tau and amyloid-beta pathology and some overlap with human AD data.

Terazosin drives sex-dependent adrenergic-bioenergetic reprogramming to restore network function in Alzheimer's disease

This study identifies terazosin as a drug that reverses AD-related molecular signatures and preserves noradrenergic circuits in a sex-dependent manner in a rat model of Alzheimer's disease.

Alpha-Synuclein Co-Pathology and Amyloid-Tau Coupling in Alzheimer's Disease: Cross-Sectional and Longitudinal Analyses Across Braak Stage Regions

This study examines how alpha-synuclein affects amyloid-tau and tau-cognition relationships in Alzheimer's disease, finding modest cross-sectional associations but no significant longitudinal effects.

AI-guided design and ex vivo validation of nanobodies targeting aggregation motifs of intrinsically disordered protein tau

The paper designs AI-guided nanobodies targeting the VQIVYK motif of tau, showing strong binding to synthetic tau and Alzheimer's brain tissue.

Deletion of TNFR1 in astrocytes restores memory in aged Alzheimer's disease mice

Deleting TNFR1 in astrocytes improves memory in aged Alzheimer's mice by rebalancing hippocampal circuitry excitability through synaptic pathway changes.

Single-Nuclei Transcriptomic Characterization of APOE4-Associated Alzheimer's Disease

This study characterizes cell-type-specific transcriptomes across APOE genotypes in Alzheimer's disease using single-nuclei RNA sequencing, revealing APOE4-associated changes in excitatory neurons and microglia.

Early peripheral immune signaling precedes tau elevation and blood-brain barrier disruption in Alzheimer's disease

Neuronal APOE4-induced Early Hippocampal Network Hyperexcitability in Alzheimers Disease Pathogenesis

This study identifies early hippocampal network hyperexcitability in APOE4 mice, linked to Nell2 overexpression, and shows its role in AD pathogenesis.

Prion protein-derived cell-penetrating peptide inhibits type II diabetes-associated islet amyloid polypeptide aggregation and cytotoxicity

This study evaluates a cell-penetrating peptide (NCAM1-PrP) for its ability to inhibit IAPP aggregation and cytotoxicity in type II diabetes.

A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimers and Parkinsons Disease

This paper uses computational techniques to analyze transcriptomic data and identify common pathways involving BAG family proteins in Alzheimer's and Parkinson's disease.

Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity

This study integrates multi-omics data from aged human brains to identify cross-system biological factors and molecular subtypes associated with Alzheimer's disease heterogeneity.

TOMM40 suppression promotes neuronal cholesterol imbalance and molecular and behavioral phenotypes of Alzheimer's disease

This study shows that TOMM40 suppression leads to cholesterol imbalance and AD-like molecular and behavioral changes in mice and human neurons.

Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model

This study investigates the impact of early locus coeruleus lesions in TgF344-AD rats and finds that LC lesions and AD genotype rarely interact to worsen deficits or neuropathology.

Tracking tau and cellular responses in human iPSC-microglia from uptake to seedable secretion in extracellular vesicles

This study shows human iPSC-derived microglia uptake and process tau fibrils, leading to secretion in extracellular vesicles that can seed tau aggregation in neurons.

Single-subject Proteomic Signatures in Alzheimers Disease Reflect Clinical Phenotypes and Distinguish Asymptomatic from Symptomatic Cases

The paper introduces INDIGO, a framework for individual-level proteomic analysis in Alzheimer's Disease, identifying molecular subgroups linked to clinical and pathological features.

Local genetic correlation analysis of Alzheimer's disease and stroke implicates PHLPP1 as a shared locus in individuals of African ancestry

Integrative Genomic and Functional Analyses Reveal NINL as a Modulator of Tau Aggregation

The paper identifies NINL as a modulator of tau aggregation through integrative genomic and functional analyses linking it to proteostasis dysfunction in FTD and AD.

Single-nucleus transcriptomics identifies a shared vulnerable excitatory neuronal population across typical and atypical Alzheimers disease

Disrupted Lipid Homeostasis as a Pathogenic Mechanism in ABCA7-Associated Alzheimers Disease Risk

This paper investigates the impact of an ancestry-specific ABCA7 deletion on lipid homeostasis in Alzheimer's disease, showing disrupted lipid regulation in neurons.

The phosphoS655 Alzheimer's Amyloid Precursor Protein (APP) interactome in neuronal differentiation

The paper identifies the phosphoS655 APP interactome in neuronal differentiation, showing it contributes to neuritogenesis through specific protein interactions.

Neurodegeneration risk variants promote lysosomal TMEM106B fibrilaccumulation

The paper identifies TMEM106B fibril accumulation as a shared mechanism in neurodegeneration linked to genetic variants in TMEM106B and GRN.