Role of the APP promoter in Alzheimer's disease: cell type-specific expression of the beta-amyloid precursor protein.
One of the major hallmarks in Alzheimer's disease (AD) is amyloid deposition in the brain of afflicted subjects. This tissue-specific deposition of the amyloid beta-protein (Abeta) is the major characteristic of AD. Abeta is proteolytically derived from a large Abeta precursor protein (APP). An apparent overexpression of the APP gene in certain areas of the AD brain indicates that abnormalities in gene regulation might be an important factor in AD pathology. The mechanism of expression of APP in different cell types is poorly understood. To understand the contribution of different cell types, such as neuronal, glial, and epithelial cells, APP expression was studied at the message and protein levels. Levels of APP expression, both message and protein, were greater in human neuroblastoma (NB) and PC12 cells than in glial and HeLa cells. DNA transfection experiments suggest that the relative activities of different promoter regions varied according to cell type. Although the upstream regulatory element in the promoter region is necessary for activity in PC12 and HeLa cells, this is not the case for NB cells. A 30-bp proximal promoter region was found to be important for cell type-specific APP gene expression.
Lahiri
Debomoy K
DK
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, USA. dlahiri@iupui.edu
Ge
Yuan-Wen
YW
D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic
D016564:Amyloid beta-Protein Precursor