GBA-associated PD. Neurodegeneration, altered membrane metabolism, and lack of energy failure.
OBJECTIVE
To elucidate possible mechanisms leading to neurodegeneration in patients with glucocerebrosidase (GBA)-associated Parkinson disease (PD) using combined proton ((1)H) and phosphorus ((31)P) magnetic resonance spectroscopic imaging (MRSI) in vivo.


METHODS
(1)H and (1)H-decoupled (31)P 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 (1)H 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.


CONCLUSIONS
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.
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Kathrin
K
Brockmann
Ruediger
R
Hilker
Ulrich
U
Pilatus
Simon
S
Baudrexel
Karin
K
Srulijes
Jörg
J
Magerkurth
Ann-Kathrin
AK
Hauser
Claudia
C
Schulte
Ilona
I
Csoti
Caroline Denise
CD
Merten
Thomas
T
Gasser
Daniela
D
Berg
Elke
E
Hattingen
D000244:Adenosine Diphosphate / Q000378:metabolism; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000465:Algorithms; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001923:Brain Chemistry; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics*; D010743:Phospholipids / Q000378:metabolism; D012984:Software
D010743:Phospholipids; D001224:Aspartic Acid; D000244:Adenosine Diphosphate; D004247:DNA; C000179:N-acetylaspartate; D005962:Glucosylceramidase; D003401:Creatine; D002794:Choline