SNCA protein fibrils are main components of Lewy bodies and glial cytoplasmic inclusions. These abnormal protein aggregates mark neurons and glia in brains affected by PD, Lewy body dementia and multiple system atrophy. Multiplications of the SNCA gene are implicated in familial PD. Several point mutations of the a-synuclein protein are associated with the development of PD. Further, several common single nucleotide variants in SNCA are associated with increased susceptibility to sporadic PD. However, the direct role that SNCA plays in the progression of PD, and the relation between SNCA and PD onset are still largely unknown. We first use an anatomically comprehensive atlas of normal brain tissue to provide a regional characterization of SNCA expression. In order to functionally associate SNCA expression, we examined its co-expression dynamics across brain regions and development. Interestingly, we find strong and significant negative co-expression between SNCA and genes that participate in immune responses, specifically genes in the interferon-gamma mediated signaling pathway. Negative co-expression with IFN-c signaling genes is highly significant and robust, and is found in each of the gene expression resources used. We examined these negative correlations over development and found a strong developmental effect. Specifically, brain-wide expression patterns of IFN-c signaling genes is increasingly opposite of SNCA over development. We tested this co-expression relationship in several gene expression datasets of PD cases, revealing a switch to positive co-expression between SNCA and IFN-c signaling genes in diseased brains. We examined co-expression patterns of SNCA in the brain, finding a strong negative correlation between SNCA and IFN-c mediated signaling genes. This relationship amplifies with age in normal brain samples. We next examined correlation patterns of SNCA and IFN-c in several transcriptomic datasets of PD and healthy brains and show a reversal of these correlations, from negative in healthy brains to positive in PD samples. Transcriptomic essays of PD samples demonstrate that the disease inflicts a global effect on patterns of gene expression. However, the genes that are differentially expressed between PD and control samples lack agreement across studies, although some consistency is found in analyses of substantia nigra samples. We show that the loss of negative correlation between SNCA and IFN-c genes is significant, specific and robust. Only a handful of genes scored show a higher specificity than SNCA, and a few of these are associated with Parkinson’s disease. Half of the six genes with larger increases in IFN-c anti-correlations across age have been previously linked to Parkinson’s. From the remaining three we note that Nucleosome assembly protein 1-like 2 and Mortality Factor 4 Like 2 function in histone acetylation. SNCA is also known to regulate histone MLN4924 citations acetylation, suggesting a broad mechanism that could downregulate the large set of IFN-c genes. Less is known about the function of the seven genes with higher co-expression changes than SNCA in studies of Parkinson’s brain.