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The exact pathway leading to neuron death and muscle atrophy in amyotrophic lateral sclerosis (ALS) has not yet been elucidated. Gene expression profile of spinal cord, blood and muscle could provide signalling pathways and systemic alterations useful for future biomarker development. In our study we compared whole genome expression profiles of lumbar spinal cord with peripheral blood and tibialis anterior muscle in 16 mutant SOD1-G93A mice and 15 wild-type littermates. In SOD1-G93A mice, 11 genes were significantly differentially expressed in spinal cord, and 16 genes in blood, while much larger transcriptional changes were noted in muscle (1745 genes significant; six overlapping with spinal cord (0.3%)) probably due to muscle atrophy. Overlap with spinal cord was enriched for significant genes in blood (six of 16 overlapping with spinal cord (37.5%)). Three genes were significantly down-regulated in all three tissues, and were closely related to mitochondrial function. Furthermore, clustering the significant genes in spinal cord and in blood, but not in muscle, could identify the SOD1-G93A mice. We conclude that blood gene expression profile overlapped with profile of spinal cord, allowing differentiation of SOD1-G93A mice from wild-type littermates. Blood gene expression profiling may be a promising biomarker for ALS patients. [ABSTRACT FROM AUTHOR]

The exact pathogenic cascade leading to motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is unknown. Gene expression profiles of ALS-affected spinal cord and motor neurons have been well established in mice and man. We provide a meta-analysis of the reported significant gene lists of gene expression studies in ALS, and compare results between mouse models and human post mortem tissue. In total, 12 articles met inclusion criteria. Twenty-nine genes were found to be differentially expressed at least twice in studies using human post mortem tissue, enriched for the functions 'immune response', 'apoptosis' and 'protein metabolism'. In mouse studies, 86 genes were reported at least two times and were enriched for 'immune response', 'lysosome', 'metal ion binding' and 'mitochondrion'. Next, all differentially expressed genes from the mouse studies were translated to human homologous genes. Seventy-four differentially expressed genes in mouse tissue were also found to be differentially expressed in human tissue. In conclusion, evidence was found for shared dysfunction in protein turnover in the ubiquitin-proteasome system. Differential expression of Cathepsin B and D, GFAP and SERPINA3 was repeatedly found to be significant in both the mouse model and ALS patients. [ABSTRACT FROM AUTHOR]