Objective: Testing the role of glycolipid accumulation in the risk for Parkinson’s disease.

Background: Increased risk for Parkinson’s disease is well known among carriers of single mutation is the GBA (glucocerebrosidase) gene and among patients with non-neuronopathic (type-1) Gaucher disease, which is caused by two trans GBA mutations. However, it remains unclear which biochemical pathways link GBA mutations with Parkinson’s disease, and what might be the role of glucosylceramide accumulation, typical in Gaucher disease but not in heterozygous carriers.

Methods: We compared the hyperechogenic area of the substantia nigra, a marker for the risk of Parkinson’s disease measured by transcranial sonography, in GBA mutation carriers (n=71) and Gaucher patients (n=145), both without Parkinson’s disease.

Results: We show that the area of hyperechogenicity is similarly enlarged in both populations relative to healthy controls (n=49). Moreover, this similarity between GBA carriers and Gaucher patients persists when comparing only carriers of the N370S (c.1226A>G) mutation (n=38) with untreated Gaucher patients, which are homozygotes to the same mutation (n=47). Measuring the blood levels of the deacylated form of glucosylceramide, glucosylsphingosine, revealed that substrate accumulation occurred only in the latter group. This sharply contrasts with our observation that the enlargement in SN hyperechogenicity area was highly similar between these two populations.

Conclusions: Glycolipid accumulation in those at-risk populations is not a significant factor in increasing the risk for Parkinson’s Disease and therefore substance reduction strategies are unlikely to play a significant role in Parkinson’s prevention.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/substantia-nigra-hyperechogenicity-is-similarly-enlarged-in-gaucher-and-in-gba-mutation-carriers/