Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain

The treatment of Alzheimer's disease (AD) remains a major challenge because of the incomplete understanding of the triggering events that lead to the selective neurodegeneration characteristic of AD brains. Here we describe a new protein, CGI-94, that is down-regulated at the mRNA level in the hippocampus of early stage AD brain. Transfection experiments with CGI-94 as a green florescent protein (GFP)-fusion-protein show that this protein is translocated into the nucleus of the cell. The finding that this protein, which has a bipartite nuclear localization signal, is also observed in the cytoplasm and extracellular space points to a multifunctional protein. Immunohistochemical analyses reveal that CGI-94 is mainly expressed in neurons of the hippocampal formation and the cortex but not in the cerebellar nucleus. In conclusion, the expression of the nucleolar phosphoprotein CGI-94 appears to be disturbed in early processes of neuronal degeneration.