AMYLOID PRECURSOR PROTEIN-FRAGMENT AND ACETYLCHOLINESTERASE INCREASE WITH CELL CONFLUENCE AND DIFFERENTIATION IN A NEURONAL CELL-LINE

This study addresses the developmental regulation of amyloid precursor protein (APP) fragments comprising the amyloid-beta peptide (A beta) and the amyloid-promoting factor acetylcholinesterase (AChE) in a mous e neuronal cell line (Neuro-2a). Results indicate that a 35-kDa amyloi dogenic fragment of APP and the major molecular forms of AChE (G(1) an d G(4)) in Neuro-2a cells significantly increase with increasing level s of cell confluence. The foregoing molecules undergo further increase s when neuroblastoma cells differentiate in the presence of dibutyryl cAMP. In contrast, a 17-kDa fragment of APP and butyrylcholinesterase mere not affected by cell confluence or differentiation. These finding s are the first to indicate that a selective A beta-containing fragmen t of APP is subject to developmental regulation. Moreover, our data sh ow that the 35-kDa fragment and AChE forms respond in parallel to the same developmental stimuli, i.e., cell confluence and differentiation. This points to the existence of a functional relationship between bot h molecules, a notion that is consistent with the potential role that has been ascribed to AChE in both APP processing and the formation of amyloid deposits in Alzheimer's brains. (C) 1996 Academic Press, Inc.