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Abstract
Objective: To elucidate possible mechanisms leading to neurodegeneration in patients with glucocerebrosidase (GBA)–associated Parkinson disease (PD) using combined proton (1H) and phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) in vivo.
Methods: 1H and 1H-decoupled 31P MRSI was performed in 13 patients with PD with heterozygous GBA mutations (GBA-PD) and 19 age- and sex-matched healthy controls to investigate metabolite concentrations in the mesostriatal target regions of PD pathology. NAA as marker of neuronal integrity, choline and ethanolamine containing compounds as markers of membrane phospholipid metabolism, and energy metabolites (notably high-energy phosphates) were quantified.
Results: Compared to controls, NAA was significantly reduced in the putamen (p = 0.012) and in the midbrain of GBA-PD (p = 0.05). The choline concentration obtained from 1H MRSI was significantly decreased in the midbrain of GBA-PD (p = 0.010). The phospholipid degradation product glycerophosphoethalonamine was increased in the putamen of GBA-PD (p = 0.05). Changes of energy metabolism were not detected in any region of interest.
Conclusion: The pattern of neurodegeneration in GBA-associated PD is more pronounced in the putamen than in the midbrain. Our MRSI findings suggest that the neurodegenerative process in GBA-PD is associated with alterations of membrane phospholipid metabolism which might be also involved in abnormal α-synuclein aggregation.
GLOSSARY
- ADP=
- adenosine diphosphate;
- ATP=
- adenosine triphosphate;
- CCT=
- phosphocholine cytidylyltransferase;
- Cr=
- creatine;
- ETS=
- electron transport system;
- GBA=
- glucocerebrosidase;
- GBA-PD=
- patients with Parkinson disease with heterozygous GBA mutations;
- GD=
- Gaucher disease;
- GM=
- gray matter;
- GPC=
- glycerophosphocholine;
- GPE=
- glycerophosphoethalonamine;
- 1H=
- proton;
- HEP=
- high-energy phosphate;
- LB=
- Lewy body;
- LEP=
- low-energy metabolite;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- MRSI=
- magnetic resonance spectroscopic imaging;
- MSA=
- multiple system atrophy;
- NAA=
- N-acetyl aspartate;
- 31P=
- phosphorous;
- PCho =
- phosphocholine;
- PCr =
- phosphocreatine;
- PD =
- Parkinson disease;
- PEth =
- phosphoethanolamine;
- Pi =
- inorganic phosphate;
- PtdCho =
- phosphatidylcholine;
- PtdSer =
- phosphatidylserine;
- SPM =
- Statistical Parametric Mapping;
- tCho =
- total choline;
- tCr =
- total creatine;
- TE =
- echo time;
- TR =
- repetition time;
- UPDRS-III =
- motor part of the Unified Parkinson's Disease Rating Scale;
- WM =
- white matter
Footnotes
Study funding: The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement 241791 European Project on Mendelian Forms of Parkinson's Disease (MEFOPA).
Editorial, page 202.
- Received August 20, 2011.
- Accepted November 28, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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