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Role of the APP Promoter in Alzheimer's Disease: Cell Type‐Specific Expression of the β‐Amyloid Precursor Protein
Author(s) -
LAHIRI DEBOMOY K.,
GE YUANWEN
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.039
Subject(s) - amyloid precursor protein , transfection , cell type , hela , biology , gene , cell , promoter , gene expression , microbiology and biotechnology , alzheimer's disease , chemistry , pathology , disease , genetics , medicine
A bstract : 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 β‐protein (Aβ) is the major characteristic of AD. Aβ is proteolytically derived from a large Aβ 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.