Differences in Cerebral Glucose Metabolism in ALS Patients with and without C9orf72 and SOD1 Mutations

Joke De Vocht; Donatienne Van Weehaeghe; Fouke Ombelet; Pegah Masrori; Nikita Lamaire; Martijn Devrome; Hilde Van Esch; Mathieu Moisse; Michel Koole; Patrick Dupont; Koen Van Laere; Philip Van Damme

doi:10.3390/cells12060933

Differences in Cerebral Glucose Metabolism in ALS Patients with and without C9orf72 and SOD1 Mutations

Cells. 2023 Mar 18;12(6):933. doi: 10.3390/cells12060933.

Authors

Affiliations

¹ Division of Psychiatry, Division of Neurology, University Hospitals Leuven, VIB-KULeuven Center for Brain & Disease Research, Laboratory of Neurobiology, Department of Neurosciences, Leuven Brain Institute (LBI), Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
² Department of Radiology and Nuclear Medicine, Ghent University Hospital, 9000 Ghent, Belgium.
³ Division of Neurology, University Hospitals Leuven, VIB-KULeuven Center for Brain & Disease Research, Laboratory of Neurobiology, Department of Neurosciences, Leuven Brain Institute (LBI), Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
⁴ Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
⁵ Center for Human Genetics, University Hospitals Leuven, 3000 Leuven, Belgium.
⁶ VIB-KU Leuven Center for Brain & Disease Research, Laboratory of Neurobiology, Department of Neurosciences, Leuven Brain Institute (LBI), Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
⁷ Laboratory of Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), Katholieke Universiteit Leuven, 3000 Leuven, Belgium.

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons. In 10% of patients, the disorder runs in the family. Our aim was to study the impact of ALS-causing gene mutations on cerebral glucose metabolism. Between October 2010 and October 2022, 538 patients underwent genetic testing for mutations with strong evidence of causality for ALS and ¹⁸F-2-fluoro-2-deoxy-D-glucose-PET (FDG PET), at University Hospitals Leuven. We identified 48 C9orf72-ALS and 22 SOD1-ALS patients. After propensity score matching, two cohorts of 48 and 21 matched sporadic ALS patients, as well as 20 healthy controls were included. FDG PET images were assessed using a voxel-based and volume-of-interest approach. We observed widespread frontotemporal involvement in all ALS groups, in comparison to healthy controls. The degree of relative glucose metabolism in SOD1-ALS in motor and extra-motor regions did not differ significantly from matched sporadic ALS patients. In C9orf72-ALS, we found more pronounced hypometabolism in the peri-rolandic region and thalamus, and hypermetabolism in the medulla extending to the pons, in comparison to matched sporadic ALS patients. Our study revealed C9orf72-dependent differences in glucose metabolism in the peri-rolandic region, thalamus, and brainstem (i.e., medulla, extending to the pons) in relation to matched sporadic ALS patients.

Keywords: C9orf72; FDG PET; SOD1; genetic ALS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis* / diagnostic imaging
Amyotrophic Lateral Sclerosis* / genetics
Amyotrophic Lateral Sclerosis* / metabolism
Brain / metabolism
C9orf72 Protein* / genetics
Fluorodeoxyglucose F18
Glucose* / metabolism
Humans
Mutation / genetics
Superoxide Dismutase-1* / genetics

Substances

C9orf72 Protein
C9orf72 protein, human
Fluorodeoxyglucose F18
SOD1 protein, human
Superoxide Dismutase-1
Glucose

Supplementary concepts

Amyotrophic lateral sclerosis 1

Grants and funding

This research was funded by Stichting Alzheimer Onderzoek (Grant nr: SAO-FRA 2021/0027), KU Leuven (Grant nr: PDMT2/21/083), University Hospitals Leuven, ALS Liga België, The Thierry Latran Foundation (INSPIRED).