Phenoconversion and disease progression observed in mutation carriers of familial Frontotemporal Lobar Degeneration in the ALLFTD Consortium

Background The ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study is designed to characterize both sporadic and familial FTLD (f-FTLD) through annual detailed clinical, neuropsychological, biomarker, neuroimaging assessments capture disease onset trajectory in preparation for therapeutic trails FTLD. Transitions from asymptomatic mild disease, or overt, may reveal critical windows intervention. Method 169 f-FTLD participants carrying mutations the main FTLD-associated genes (79 C9orf72; 37 GRN; 53 MAPT) with at least two clinical were included analysis of phenoconversion disease. [CDRÒ + NACC global scores (Miyagawa et al, 2020) used define baseline status first visit: “asymptomatic” = 0 “mild” 0.5. Conversion was defined as “partial” (asymptomatic mild), “definite” overt > 1) “mild overt” (0.5 1). Result Definite conversion occurred most often MAPT mutation carriers, 5/43 carriers transitioning across multiple visits. also seen 2/65 C9orf72 expansion 1/30 GRN carriers. All definite converters assessed (CDRÒ 0.5) one intermediate visit; observed 2-4 years initial assessment. Partial conversions all three genetic groups (MAPT: 6; C9orf72: 5; GRN: 5). Further expected be these additional follow-up less likely progress a (3/14) than (4/6) (7/10). Conclusion assessment natural history studies can early mutations; corresponding imaging, cognitive, biomarker profiles captured provide insights into mechanisms trajectories.