Presynaptic dopamine transporter binding defect in essential tremor plus associated with GBA1 variants

Abstract

Essential tremor (ET) is a movement disorder that has associations with Parkinson’s disease, but the details of this connection remain poorly understood. A subgroup of ET, “ET plus” with atypical clinical features such as cognitive dysfunction and gait difficulty, has been recently proposed. To elucidate the potential associations of ET plus and PD, we investigated clinically and with DAT imaging a group of 98 PD patients and a group of 36 ET plus patients. To evaluate the potential role of GBA pathway in these conditions, we analysed four common PD-associated GBA1 variants (p.Asn409Ser, p.Leu483Pro, p.Glu365Lys, and p.Thr408Met) in both groups. We found no difference in clinical features or in DAT binding between PD patients harbouring GBA1 variants and those without. Surprisingly, the prevalence of GBA1 variants did not differ between patients with PD and patients with ET plus. Among the ET plus patients with GBA1 variants, there was a trend toward lower DAT binding in the left anterior and right posterior putamen compared to patients with non-GBA-ET plus, however after correcting for age this did not remain significant. Our findings suggest that GBA1 variants may play a role in ET plus, that shares both clinical and pathophysiological features with PD. The role of GBA1 in parkinsonian phenotypes differing from PD merits further studies.