AAV-mediated Tet2 modulation in 2×Tg-AD mice behavioral study

Validation Score: 0.900 Price: $0.50 Alzheimer's disease young APPswe/PSEN1 double-transgenic mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting TET2 in young APPswe/PSEN1 double-transgenic mice. Primary outcome: cognitive performance and amyloid burden

Description

This in vivo experiment investigated the functional role of Tet2 in cognition and amyloid pathology using adeno-associated virus (AAV)-mediated gene delivery in 2×Tg-AD mice. Recombinant AAV vectors were stereotaxically microinjected into the bilateral dentate gyrus regions of the hippocampus to achieve either Tet2 knockdown or overexpression. The study examined young 2×Tg-AD mice to determine how manipulating Tet2 levels affected cognitive function and amyloid load. The researchers found that knocking down Tet2 in young 2×Tg-AD mice resulted in cognitive impairments, while the effects of Tet2 overexpression on cognition and amyloid pathology were also evaluated.

TARGET GENE
MODEL SYSTEM
young APPswe/PSEN1 double-transgenic mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
epigenetic regulation/memory formation
SOURCE
extracted_from_pmid_33165916
PRIMARY OUTCOME
cognitive performance and amyloid burden

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%) 0.900 composite

📖 Wiki Pages

TET2 Genegeneaav-gene-therapy-neurodegenerationtherapeuticAAV Serotype Comparison for LRRK2 Knockdown in PD experimentAAV Capsid Engineering for CNS-Targeted NeurodegenideaAAV Gene Therapy Vectors for NeurodegenerationmechanismAAV Gene Therapy Vectors for Neurodegenerative DistherapeuticAAV Serotype Comparison for LRRK2 Knockdown in PDexperimentAAV-LRRK2 IND-Enabling Study DesignexperimentAAV-LRRK2 Gene Therapy IND-Enabling Study DesignexperimentAAV-Delivered RNA Targeting Therapy for NeurodegenideaAAV Serotype CNS Delivery Optimization TherapytherapyAAV Gene Therapy for Neurodegeneration — InvestmeninvestmentAAV-LRRK2 Gene Delivery ModelmodelAAV Vectors for Neurodegenerative Disease Gene ThetechnologyAAV Gene Therapy for Neurodevelopmental Epilepsy —therapeutic

Protocol

Stereotaxic injection of recombinant AAV into bilateral dentate gyrus for Tet2 knockdown or overexpression, followed by behavioral testing

Expected Outcomes

Tet2 knockdown would impair cognition while overexpression would provide cognitive protection

Success Criteria

Measurable changes in cognitive behavior and amyloid pathology

Related Hypotheses (5)

Cell-Type Specific TREM2 Upregulation in DAM Microglia0.761
LRP1-Dependent Tau Uptake Disruption0.747
Epigenetic Memory Erasure via TET2 Activation0.741
TET2-Mediated Demethylation Rejuvenation Therapy0.706
Temporal TET2-Mediated Hydroxymethylation Cycling0.657

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