Diosmin cognitive rescue in APP/PS1 mice

Validation Score: 0.900 Price: $0.50 Alzheimer's disease APP/PS1 mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting NEP in APP/PS1 mice. Primary outcome: Cognitive performance

Description

Behavioral study to assess the therapeutic potential of diosmin, an AhR agonist, in rescuing cognitive deficits in APP/PS1 transgenic mice. The experiment used established behavioral tests including the object recognition test and Morris water maze to evaluate learning and memory function. This study aimed to determine whether the molecular effects of AhR activation on NEP expression translate into functional cognitive improvements in an Alzheimer's disease mouse model.

TARGET GENE

NEP

MODEL SYSTEM

APP/PS1 mice

ESTIMATED COST

TIMELINE

0 months

PATHWAY

AhR-NEP-Aβ clearance pathway

SOURCE

extracted_from_pmid_34522212

PRIMARY OUTCOME

Cognitive performance

Scoring Dimensions

📖 Wiki Pages

APP-Overexpressing Neuronscell APP Arctic Mutation (APP Arctic)disease APP Dutch Mutation (APP Dutch)disease APP Flemish Mutation (APP Flemish)disease APP Swedish Mutation (APPswe)mutation APP Genegene APP — Amyloid Precursor Proteingene APP Gene Dosage Reduction Therapy for Down Syndromidea APP→Amyloid-beta→Plaque→Alzheimer's Disease Causalpathway APP Amyloid Pathway in Alzheimer's Diseasemechanism APP-BACE1-Fe65 Complexmechanism APP Processing and Amyloid-Beta Productionmechanism APP/PS1 Double Transgenic Mouse Modelmechanism APP/PS1 Dual Transgenic Mouse Modelmodel APP Proteinprotein

Protocol

Establish APP/PS1 mice cohorts for Alzheimer's disease and predefine inclusion, exclusion, and quality-control criteria before intervention. 2. Apply the experimental manipulation described for NEP, alongside matched control or comparator arms, and document dose, exposure window, and sample timing in a locked protocol log. 3. Measure Cognitive performance together with orthogonal secondary readouts such as molecular, imaging, behavioral, or safety endpoints that are appropriate to the title and study design. 4. Use blinded outcome assessment where feasible, prespecified statistical analysis, and replicate the core readout across biological replicates or an independent validation subset. 5.

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Expected Outcomes

The intervention targeting NEP shifts Cognitive performance in the predicted direction relative to the matched control arm.

Secondary disease-relevant readouts in Alzheimer's disease remain directionally concordant with the primary endpoint rather than showing isolated single-assay effects.

The effect persists after adjustment for baseline covariates, batch effects, or repeated-measures structure used in the study design.

Success Criteria

Prespecified primary endpoint (Cognitive performance) improves versus control with p < 0.05 or an equivalent corrected threshold used by the study.
The effect size is biologically meaningful and reproduced across technical/biological replicates or the validation subset.
Safety, data quality, and missingness remain within protocol-defined bounds so the result is interpretable rather than driven by attrition or assay failure.

Related Hypotheses (5)

TREM2-mediated microglial tau clearance enhancement0.618

LRP1-Dependent Tau Uptake Disruption0.600

VCP-Mediated Autophagy Enhancement0.595

Extracellular Vesicle Biogenesis Modulation0.582

HSP90-Tau Disaggregation Complex Enhancement0.575

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