SUMMARY
# Prion Strain Diversity and Selective Vulnerability
## Background and Rationale
Prion diseases represent a unique category of neurodegenerative disorders characterized by the misfolding and aggregation of the prion protein (PrP), leading to progressive neurodegeneration. Recent evidence suggests that prion-like mechanisms may contribute to Alzheimer's disease pathology through tau and amyloid-β protein propagation. This study investigates prion strain diversity and selective vulnerability patte
METHODOLOGY NOTES
Phase 1 (Weeks 1-2): Prepare transgenic mice (n=60 per strain group, 3-4 months old) expressing human tau and APP. Acclimate animals and perform baseline cognitive testing using Morris water maze and Y-maze. Phase 2 (Week 3): Intracerebral inoculation of prion strains - 22L, ME7, RML strains (20μL, 10^6 ID50 units) via stereotactic injection into hippocampus. Control groups receive PBS injection. Phase 3 (Weeks 4-20): Monthly behavioral assessments including rotarod performance, open field activity, and cognitive testing. Collect blood samples biweekly for RT-QuIC analysis of circulating prion seeds. Phase 4 (Weeks 21-40): Sacrifice subgroups (n=10 per timepoint) at 21, 28, 35, and 40 weeks post-inoculation. Perform transcardial perfusion with 4% paraformaldehyde. Phase 5 (Weeks 41-44): Tissue processing and analysis - brain sectioning for immunohistochemistry (PrP, tau, Aβ antibodies), RT-QuIC assays on brain homogenates, Western blot analysis for protein aggregation, and stereologica