Neurochemical changes in presymptomatic C9orf72-HRE frontotemporal lobar degeneration: a 7T magnetic resonance spectroscopy study

Motivation: Frontotemporal lobar degeneration is a neurodegenerative disorder with atrophy and protein accumulation most prominently in the frontal and temporal lobes. Neuroinflammation is involved in the disease process, but the timing and role are unclear. Goal(s): Our aim is to study neurodegenerative and neuroinflammatory changes in patients, presymptomatic carriers, and controls. Approach: In this preliminary analysis, we used ultrahigh-field ¹H-MRS in presymptomatic C9orf72-carriers (n=14), and controls (n=17). Results: We found a significant reduction in the neuronal marker (NAA/tCr) in the C9orf72 carriers compared to controls. We will continue data acquisition to expand statistical analysis to the full cohort, including patients, presymptomatic carriers, and controls. Impact: This is the first study to use 7T MRS in presymptomatic carriers of the C9orf72-repeat expansion. We found decreased N-acetyl-aspartate/total creatine ratio, suggesting neuronal viability loss before symptom onset, whereas we found no signs of presymptomatic neuroinflammation.