SUMMARY
# Brain Connectivity-Targeted tACS Trial in Early AD
## Background and Rationale
Alzheimer's disease (AD) represents a complex neurodegenerative disorder characterized not only by the hallmark pathological accumulations of amyloid-beta plaques and tau neurofibrillary tangles, but increasingly recognized for its profound disruption of neural network function. Emerging evidence from resting-state functional magnetic resonance imaging (rs-fMRI) studies reveals that early-stage AD is marked by aberr
METHODOLOGY NOTES
## PROTOCOL
**Phase 1: Pre-intervention Characterization and Baseline Assessment (Weeks -4 to 0)**
Recruit a cohort of 48 transgenic AD model mice (APP/PS1 or 5xFAD line, 5-6 months old, n=24 intervention, n=24 controls) with confirmed early-stage amyloid-beta pathology validated via in vivo two-photon microscopy and plasma biomarkers (phospho-tau181, phospho-tau217). Perform comprehensive baseline neurophysiological profiling including: (1) resting-state functional magnetic resonance imaging (rs-fMRI) at 9.4T with 200 µm isotropic resolution to map default mode network (DMN) connectivity patterns, (2) electrophysiological recordings from prefrontal cortex (PFC), hippocampal CA3-CA1, and posterior cingulate cortex (PCC) using 32-channel silicon probes to characterize baseline oscillatory dynamics and cross-regional coherence in theta (4-12 Hz), gamma (30-100 Hz), and sleep spindle (10-16 Hz) bands, (3) Morris water maze testing for spatial reference memory (acquisition: 4 days, 6 tri