Low Glucocerebrosidase Activity Predicts Dementia in Parkinson Disease: Less Is Not More!

For a long time, there has been a recognized link between GBA gene sequence variants and risk of Parkinson disease (PD). In fact, Neurology® published an editorial 14 years ago by Rogaeva and Hardy¹ on this topic. The GBA gene, also known as glucosylceramidase β, encodes the lysosomal membrane protein called glucocerebrosidase (GCase). GCase is responsible for breaking down the molecule glucosylceramide. GBA gene sequence variants lead to loss of GCase activity, which results in uncontrolled accumulation of glucosylceramide. As a downstream effect, loss of GCase activity has been linked to α-synuclein aggregation, a key pathologic mechanism of PD.² This suggests that GCase activity may be an important biological factor in PD clinical research.

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