Lack of evidence for genetic association of saposins A, B, C and D with Parkinson ’s disease

We read with much interest the paper byOjiet al. (2020), which suggested an association between mutations in the saposin D region ofPSAP and Parkinson ’s disease. In their paper, the authors showed that variants in saposin D only partially segregate with Parkinson’s disease in three families of Japanese origin. For example, in Family 1, at least three carriers of thePSAP p.Q453P variant did not have Parkinson ’s disease, including one of the parents who was an obligate carrier. The authors also report an association of six common intronic variants within the saposin D region of the gene when comparing Japanese Parkinson’s disease patients and East Asian control subjects. Among these six variants, rs4 747203 and rs885828 remained significant also when comparing the combined Japanese-Taiwanese Parkinson’s disease cohorts with East Asian controls. These two variants are in perfect linkage disequilibrium (LD, r2 = 1) in East Asians and represent the same allele. The authors further demonstrated, using different models, thatPSAP mutations may affect prosaposin localization in the lysosome, autophagy, progressive motor decline in mice, and that patient-derived fibroblasts and dopaminergic neurons had α-synuclein accumulation.

Source: Brain - August 13, 2020 Category: Neurology Source Type: research