FAC1, A NOVEL GENE IDENTIFIED WITH THE MONOCLONAL-ANTIBODY ALZ50, IS DEVELOPMENTALLY-REGULATED IN HUMAN BRAIN

The monoclonal antibody Alz50 recognizes both neurofibrillary pathology associated with Alzheimer's disease and subplate neurons in the developing human brain. To attempt to identify Alz50 antigens expressed during development, a human fetal brain cDNA library was immunoscreened. A positive clone was isolated and sequenced. The clone represents a novel gene named FAC1 (Fetal Alz-50-Reactive Clone 1). The FAC1 gene is located on human chromosome 17 and is conserved across species. In the human fetal brain, the FAC1 gene product is abundantly expressed and the protein is located both in the nucleus and the cytoplasm of cells throughout the developing cortex. Decreased levels of FAC1 protein are observed in adult brain by immunoblot analysis. By immunocytochemistry, the FAC1 protein is almost exclusively localized in the nucleus of neurons in the adult neocortex. Therefore, expression of the FAC1 gene is developmentally regulated and the cellular localization of the protein product is altered during development.