Adoptive transfer of TCRAβ-Tregs in AD mouse model

Validation Score: 0.900 Price: $0.50 Alzheimer's disease transgenic mice expressing chimeric mouse-human APP and mutant human presenilin-1 Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting APP, PSEN1 in transgenic mice expressing chimeric mouse-human APP and mutant human presenilin-1. Primary outcome: amyloid load reduction and cognitive improvement

Description

This experiment tested the therapeutic efficacy of engineered TCRAβ-Tregs in a transgenic mouse model of Alzheimer's disease. Mice expressing chimeric mouse-human amyloid precursor protein and mutant human presenilin-1 received adoptive transfer of the engineered TCRAβ-Tregs. The study measured multiple outcomes including behavioral performance, immune responses, and immunohistochemical markers. Key findings included sustained immune suppression, reduced microglial activation, decreased amyloid loads, and improved cognitive functions. 18F-fluorodeoxyglucose labeling was used to track the TCRAβ-Tregs, demonstrating their ability to home to the brain and provide antigen-specific targeting. The results showed that TCRAβ-Tregs could reduce amyloid burden, restore brain homeostasis, and improve learning and memory compared to controls.

TARGET GENE
APP, PSEN1
MODEL SYSTEM
transgenic mice expressing chimeric mouse-human APP and mutant human presenilin-1
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
amyloid processing pathway, neuroinflammation, T cell regulation
SOURCE
extracted_from_pmid_38111016
PRIMARY OUTCOME
amyloid load reduction and cognitive improvement

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

PSEN1 Protein (Presenilin-1)proteinAPP ProteinproteinAPP/PS1 Dual Transgenic Mouse ModelmodelPSEN1 Presenilin 1 AD Causal ChainmechanismAPP/PS1 Double Transgenic Mouse ModelmechanismAPP Processing and Amyloid-Beta ProductionmechanismAPP-BACE1-Fe65 ComplexmechanismAPP Amyloid Pathway in Alzheimer's DiseasemechanismAPP→Amyloid-beta→Plaque→Alzheimer's Disease CausalpathwayAPP Gene Dosage Reduction Therapy for Down SyndromideaPSEN1 — Presenilin 1geneAPP — Amyloid Precursor ProteingenePSEN1 (Redirect)redirectAPP GenegenePSEN1 Mutations in Alzheimer's Diseasedisease

Protocol

Adoptive transfer of TCRAβ-Tregs followed by behavioral testing, immunohistochemistry, and 18F-FDG tracking

Expected Outcomes

Reduced amyloid burden, decreased neuroinflammation, improved cognitive function

Success Criteria

Significant reduction in amyloid load and improved performance on cognitive tests

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