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Abstract #3144

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

Fieke Prinse1,2, Louise van der Weerd2,3, Itamar Ronen4, Harro Seelaar1, John van Swieten1, Chloé Najac2, and Elise Dopper1
1Alzheimer Center, dept. of Neurology, Erasmus Medical Center, Rotterdam, Netherlands, 2C.J. Gorter Center for MRI, dept. of Radiology, Leiden University Medical Center, Leiden, Netherlands, 3dept. of Human Genetics, Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands, 4Clinical Imaging Science Centre, Brighton and Sussex Medical School, Brighton, United Kingdom

Synopsis

Keywords: Dementia, Spectroscopy, High-field MRI

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.

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