SUMMARY
# Experimental: CAAR-T Cell Therapy for Autoantibody-Mediated Neurotoxicity in AD
## Background and Rationale
Alzheimer's disease (AD) is characterized by progressive neurodegeneration, with emerging evidence suggesting that autoantibodies targeting neuronal antigens contribute to disease pathology beyond amyloid-beta accumulation. Pathogenic autoantibodies against BACE1, AQP4, and various neuronal surface proteins have been detected in AD patients and correlate with cognitive decline and synapt
METHODOLOGY NOTES
Phase I: Screening and enrollment of 24 mild-to-moderate AD patients (MMSE 18-26) with confirmed serum levels of anti-BACE1, anti-AQP4, or anti-neuronal autoantibodies ≥2-fold above healthy controls. Patients undergo comprehensive baseline assessments including neuropsychological testing, MRI, CSF collection, and immune profiling. Phase II: CAAR-T cell manufacturing involves leukapheresis followed by T cell isolation, transduction with lentiviral vectors encoding target-specific CAARs, and ex vivo expansion for 10-14 days with quality control testing. Phase III: Dose escalation using 3+3 design with three cohorts receiving 1×10^6, 3×10^6, or 1×10^7 CAAR-T cells/kg via intravenous infusion following lymphodepleting chemotherapy (fludarabine 25mg/m² and cyclophosphamide 250mg/m² for 3 days). Phase IV: Intensive safety monitoring for 28 days including daily vital signs, cytokine release syndrome assessment, and neurological evaluations. Phase V: Long-term follow-up for 12 months with mont