Frontal and Temporal Lobe Selective Vulnerability in FTD — Mechanisms and Therapeutic Targets

SUMMARY

# Frontal and Temporal Lobe Selective Vulnerability in FTD — Mechanisms and Therapeutic Targets ## Background and Rationale This validation study investigates the molecular and cellular mechanisms underlying the selective vulnerability of frontal and temporal brain regions in frontotemporal dementia (FTD). The preferential degeneration of these areas suggests region-specific factors that predispose neurons to tau and TDP-43 pathology. This study combines post-mortem brain tissue analysis with ad

METHODOLOGY NOTES

**Phase 1: Patient Recruitment and Stratification (Months 1-6)** • Recruit 180 participants: 60 FTD patients (behavioral variant and semantic variant), 60 Alzheimer's disease controls, 60 healthy controls • Inclusion criteria: Clinical diagnosis per international consensus criteria, Mini-Mental State Examination score ≥15 for patients • Exclusion criteria: Co-morbid psychiatric disorders, substance abuse, contraindications to MRI • Obtain informed consent and complete comprehensive neuropsychological battery • Collect blood samples for genetic analysis (C9orf72, GRN, MAPT mutations) **Phase 2: Multi-Modal Neuroimaging Acquisition (Months 4-12)** • Structural MRI: High-resolution T1-weighted imaging (1mm³ voxels) for cortical thickness analysis • Diffusion tensor imaging: 64-direction protocol for white matter integrity assessment • Resting-state fMRI: 10-minute acquisitions for functional connectivity mapping • PET imaging subset (n=90): [18F]AV-1451 tau PET and [11C]PIB amyloid PET •