Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for GBA‐related Parkinson's disease
Background and purpose Individuals with GBA (glucocerebrosidase) mutations are at increased risk of Parkinson's disease (PD). It is still debated, however, whether this increased risk results from impaired glucocerebrosidase activity leading to substrate accumulation. Comparing the presence of...
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Published in | European journal of neurology Vol. 26; no. 7; pp. 1013 - 1018 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
John Wiley & Sons, Inc
01.07.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Background and purpose
Individuals with
GBA
(glucocerebrosidase) mutations are at increased risk of Parkinson's disease (PD). It is still debated, however, whether this increased risk results from impaired glucocerebrosidase activity leading to substrate accumulation. Comparing the presence of prodromal PD marker in
GBA
mutation carriers and patients with Gaucher disease (GD) (in which substrate accumulation is extensive) can assist in clarifying this issue.
Methods
In this cross‐sectional study, we compared the hyperechogenic area of the substantia nigra, a prodromal PD marker, in large cohorts of
GBA
mutation carriers (n = 71) and patients with GD (n = 145). Our control populations were healthy, non‐carriers (n = 49) and patients with
GBA
‐related PD (n = 11). Substrate accumulation was assessed from dry blood spot levels of glucosylsphingosine.
Results
Our findings indicate no contribution of substrate accumulation, as the area of hyperechogenicity is similarly enlarged relative to healthy controls in both
GBA
mutation carriers and patients with GD. Moreover, this similarity between
GBA
carriers and patients with GD persists when comparing only carriers of the N370S (c.1226A>G) mutation (n = 38) with untreated patients with GD who were homozygotes for the same mutation (n = 47). In addition, measurements of hyperechogenic area did not correlate with levels of glucosylsphingosine in the untreated patients with GD.
Conclusion
The presence of a marker of prodromal PD (substantia nigra hyperechogenicity) is independent of substrate accumulation in a population with mutated
GBA
. Although further longitudinal studies are needed to determine the precise predictive value of this marker for
GBA
‐related PD, our findings raise doubts regarding the contribution of substance reduction strategies to PD prevention. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1351-5101 1468-1331 |
DOI: | 10.1111/ene.13927 |