The letter by Papapetropoulos and colleagues presents an additional study correlating ␣-synuclein expression levels and sporadic PD. Previously we and others published studies of mRNA levels of SNCA in PD brains that have been performed using different methods. Some are in agreement with our results, while others contradict our findings. Recognizing the contradictory findings in the field, our paper explained that there were technical issues that arose in the course of these kinds of studies and emphasized the need to carefully control these assays. Thus the conclusion from Papapetropoulos et al. study to be cautious when analyzing gene expression align perfectly with our previous recommendation to be cautious when designing assays for quantifying mRNA levels since results can also reflect other factors (i.e., cell type, tissue status, studied group, assay used). In this light we believe that increased reproducibility of results can best be achieved by independent analysis of replicate samples to improve the interpretation of results and recommend that others working in this field follow our recommendations. Moreover, the internal controls for these studies have to be carefully chosen, keeping in mind the cell type heterogeneity (neurons, glia) of the tissue and the specific neuronal loss in the PD samples. This is why we chose a neuronal mRNA as an internal control for our studies. The results presented by Papapetropoulos et al. may reflect the use of a ubiquitously expressed gene, 18S rRNA, as an internal control in a heterogenous tissue that undergoes neuron-specific degeneration. The decrease in SNCA-mRNA expression might result from the neuronal loss in the substantia nigra and amygdala of PD brains. Finally, we would like to emphasize that we showed an increase in SNCA-mRNA in the majority, but not in all, sporadic PD mid-brain samples we analyzed. Thus, elevation in SNCA-mRNA levels might contribute to disease pathogenesis in many but, perhaps, not all cases of sporadic PD. Our observation is consistent with the hypothesis that an increase in SNCA expression may be a contributory factor, among other factors, to the development of at least some cases of sporadic PD.