Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by a variety of factors. Growing evidence shows that prior to the motor phase of PD can express molecular or imaging markers. Many long non-coding RNAs (lncRNAs) have been identified in neurodegenerative disease. However, the biogenesis and function of lncRNAs in the pre-symptomatic stage of PD is poorly understood. Here, we profiled the expression of lncRNAs and mRNAs in the substantia nigra pars compacta (SNpc) of pre-symptomatic mice over-expressing human A30P*A53T α-synuclein by microarray analysis. Based on the Pearson correlation analysis, lncRNA/mRNA co-expression network was constructed. GO enrichment and pathway analysis of lncRNAs–coexpressed mRNAs was conducted to identify the related biological function and pathologic pathways. Real-time PCR was used to detect the expression pattern of lncRNAs. Approximately 756 lncRNAs were aberrantly expressed in the SNpc of early over-expressing human A30P*A53T α-synuclein transgenic mice, including 477 downregulated lncRNAs and 279 upregulated lncRNAs. GO analysis indicated that these lncRNAs–coexpressed mRNAs were targeted to regulation of transcription (ontology: biological process), membrane (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis indicated that lncRNAs–coexpressed mRNAs were mostly enriched in axon guidance signaling pathway. In conclusion, the present study firstly identified a series of novel early PD-associated lncRNAs caused by mutant α-synuclein. Further study the function of these aberrantly expressed lncRNAs may provide insight into treatment of early PD.