SIRPα modulation in mouse models of Alzheimer's disease

Validation Score: 0.900 Price: $0.50 Alzheimer's disease mouse models of Alzheimer's disease Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting SIRPα in mouse models of Alzheimer's disease. Primary outcome: synaptic loss, microglial engulfment, cognitive impairment

Description

This experiment involved modulating microglial SIRPα expression in established mouse models of Alzheimer's disease to investigate its role in neurodegeneration. The researchers examined the effects of altered SIRPα expression on synaptic loss, microglial engulfment activity, and cognitive function. This comprehensive study measured multiple outcomes including synaptic integrity, microglial phagocytosis, and behavioral performance to understand how SIRPα regulates synaptic pruning in the context of neurodegeneration.

TARGET GENE
SIRPα
MODEL SYSTEM
mouse models of Alzheimer's disease
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
CD47-SIRPα signaling pathway, complement pathway
SOURCE
extracted_from_pmid_33795678
PRIMARY OUTCOME
synaptic loss, microglial engulfment, cognitive impairment

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

MicrogliacellAgitation in Alzheimer's DiseasediseaseAlzheimer's DiseasediseaseAlzheimer's DiseasediseaseAlzheimer's Disease Genetic VariantsdiseaseAlzheimer's Disease vs Parkinson's Disease ComparidiseaseAPP Mutations in Alzheimer's DiseasediseaseDLB, Parkinson's Disease, and Alzheimer's Disease:diseaseEarly-Onset Alzheimer's Disease (EOAD)diseaseInvestment Landscape: Alzheimer's DiseasediseaseNeurodegenerationdiseasePreclinical Alzheimer's DiseasediseaseProdromal Alzheimer's DiseasediseasePSEN1 Mutations in Alzheimer's DiseasediseasePSEN2 Mutations in Alzheimer's Diseasedisease

Protocol

Modulation of microglial SIRPα expression in Alzheimer's disease mouse models followed by assessment of synaptic loss, microglial engulfment activity, and cognitive testing

Expected Outcomes

Loss of microglial SIRPα results in increased synaptic loss, enhanced microglial engulfment, and worsened cognitive impairment

Success Criteria

Significant increases in synaptic loss and cognitive deficits in mice with reduced microglial SIRPα

Related Hypotheses (5)

Optogenetic restoration of hippocampal gamma oscillations via selective PV interneuron activation us0.863
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degeneration in Alzheimer0.801
Microglial TREM2 downregulation impairs damage-associated response in late-stage Alzheimer's disease0.628
TREM2-mediated microglial tau clearance enhancement0.594
LRP1-Dependent Tau Uptake Disruption0.576

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