VPS35-Linked Parkinson’s Disease Resembles the Idiopathic Disease: A Review of Clinical Trials

Abstract

A new autosomal dominant Parkinson´s disease mutation in the VPS35 (Vacuolar sorting protein 35) gene has been discovered in 2011. The VPS35 gene encodes a key component of the membrane protein-recycling retromer complex. Consequences of the D620N mutation and retromer dysfunction are perturbations in organelle/ vesicle trafficking, recycling and turnover which may result in reduction of cellular survival and gain of α-synuclein accumulation via impaired lysosomal function. VPS35-linked PD resembles the idiopathic disease. In reported cases symptoms were unilateral at the beginning in most cases and progression was slow. Initial symptoms were tremor, bradykinesia, rigidity and postural instability. Resting tremor, rigidity and bradykinesia were dominant. Almost every patient showed good response to levodopa. The frequency of VPS35 PD cases has been estimated to be rare. Until now data are missing on whether the VPS35 variant is associated with classical Lewy body pathology in the brainstem or not. We need more human case reports including neuropathology to find a specific clinical marker of VPS35 patients to allow a targeted referral to genetic testing.