SCG10, a neuron-specific growth-associated protein in Alzheimer's disease

Neuronal growth-associated proteins (nGAPs) are markers of neuronal process outgrowth and are associated with both degenerative and sprouting responses in Alzheimer's disease (AD) brain. To study possible involvement of SCG10, an nGAP, in AD, we cloned human SCG10 cDNA and analyzed SCG-10 at mRNA and protein levels in control and AD brains. The deduced amino acid sequence of human SCG10 was 69% identical to stathmin, another nGAP. By in situ hybridization, both SCG10 and stathmin mRNAs were detected in selected neuronal populations in aged human brains. Quantitative analysis by RNase protection revealed that levels of neither SCG10 nor stathmin mRNAs were significantly altered in AD. Using an SCG10-specific antibody, Western blot analysis did not reveal any quantitative changes of SCG10 in AD. However, when the concentration of SCG10 protein was plotted against the number of tangles, a positive correlation was found. SCG10 levels did not correlate with plaque numbers. Furthermore, immunohistochemical study revealed that neuronal SCG10 protein accumulated in the cell bodies in AD-affected regions. Thus, SCG10 compartmentalization and metabolism may be altered in AD possibly due to mechanisms related to tangle formation in this disease.