Pre-Symptomatic Tau Detection in MAPT Mutation Carriers

SUMMARY

# Pre-Symptomatic Tau Detection in MAPT Mutation Carriers ## Background and Rationale Mutations in the microtubule-associated protein tau gene (MAPT) cause familial frontotemporal dementia with predictable disease progression, offering a unique window for early detection and intervention. This clinical study investigates whether blood-based tau biomarkers can detect pathological changes 5-10 years before clinical symptom onset in MAPT mutation carriers. The experimental design follows presymptom

METHODOLOGY NOTES

**Phase 1: Participant Recruitment and Baseline Assessment (Months 1-6)** • Recruit 200 asymptomatic MAPT mutation carriers (P301L, R406W, V337M variants) aged 25-50 years • Recruit 100 age-matched controls without MAPT mutations • Obtain informed consent and collect detailed family history • Perform comprehensive neurological examination using ALS Functional Rating Scale-Revised (ALSFRS-R) • Conduct cognitive assessment battery including Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) • Collect baseline blood samples (20mL) in EDTA tubes for biomarker analysis **Phase 2: Longitudinal Blood Biomarker Collection (Months 1-60)** • Collect blood samples every 6 months for 5 years (11 timepoints total per participant) • Process samples within 2 hours: centrifuge at 2000g for 10 minutes, aliquot plasma • Store plasma at -80°C until batch analysis • Measure plasma tau species using Single Molecule Array (Simoa) technology: - Total tau (t-tau) - Phosphorylated