Anti-ASC antibody intracerebroventricular injection in APP/PS1 mice

Validation Score: 0.950 Price: $0.50 Alzheimer's disease APP/PS1 transgenic mice (8 months old) Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting ASC in APP/PS1 transgenic mice (8 months old). Primary outcome: Cognitive function and AD-like pathology markers

Description

This experiment evaluated the therapeutic potential of ASC-targeting antibodies in vivo using eight-month-old APP/PS1 transgenic mice, which are an established mouse model of Alzheimer's disease. The mice received intracerebroventricular (lateral ventricle) injections of either anti-ASC N-terminal antibodies or anti-ASC C-terminal antibodies. The study comprehensively assessed cognitive function through behavioral testing and examined multiple aspects of AD-like pathology including amyloid-β deposition, tau hyperphosphorylation, and neuroinflammation. This experiment aimed to determine whether the neuroprotective effects observed in cell culture could translate to improved outcomes in a living animal model, and whether targeting different domains of ASC would have differential therapeutic effects.

TARGET GENE
ASC
MODEL SYSTEM
APP/PS1 transgenic mice (8 months old)
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
ASC-mediated inflammasome pathway, amyloid processing pathway, tau phosphorylation pathway
SOURCE
extracted_from_pmid_41707905
PRIMARY OUTCOME
Cognitive function and AD-like pathology markers

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.950 composite

📖 Wiki Pages

ASC (PYCARD)geneAPP/PS1 Double Transgenic Mouse ModelmechanismAPP Dutch Mutation (APP Dutch)diseaseAPP — Amyloid Precursor ProteingeneAPP Amyloid Pathway in Alzheimer's DiseasemechanismAPP Processing and Amyloid-Beta ProductionmechanismAPP-Overexpressing NeuronscellAPP Flemish Mutation (APP Flemish)diseaseAPP GenegeneAPP Swedish Mutation (APPswe)mutationAPP Gene Dosage Reduction Therapy for Down SyndromideaAPP→Amyloid-beta→Plaque→Alzheimer's Disease CausalpathwayAPP Arctic Mutation (APP Arctic)diseaseAPP-BACE1-Fe65 ComplexmechanismAPP/PS1 Dual Transgenic Mouse Modelmodel

Protocol

Intracerebroventricular administration of anti-ASC N-terminal or C-terminal antibodies to APP/PS1 mice, followed by cognitive behavioral testing and neuropathological assessment including Aβ deposition, tau hyperphosphorylation, and neuroinflammation markers

Expected Outcomes

Improved cognitive function and reduced AD pathology following ASC antibody treatment

Success Criteria

Significant improvement in cognitive performance and reduction in Aβ plaques, tau pathology, and neuroinflammation compared to control mice

Related Hypotheses (5)

Cell-Type Specific TREM2 Upregulation in DAM Microglia0.761
OPC differentiation blockade contributes to white matter degeneration in early-stage AD0.599
TREM2-mediated microglial tau clearance enhancement0.594
LRP1-Dependent Tau Uptake Disruption0.576
Extracellular Vesicle Biogenesis Modulation0.558

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