Alzheimer's disease (AD) is characterized by depositions of the amyloid beta-peptide (Aβ) in the form of cerebrovascular amyloid and extracellular plaques. Aβ of 39-43 amino acid residue is derived from a family of larger beta-amyloid precursor proteins (βAPP) of 695-770 amino acid residue. A group of proteases generate carboxyl-truncated soluble derivatives of βAPP (sAPP) that are secreted in the conditioned medium of cell cultures and human plasma and in cerebrospinal fluid. Different factors that regulate depositions of amyloid are central to understanding the cerebrovascular changes in AD. This disease is also marked by the dramatic loss of cholinergic neurons that project to the cortex and neurochemically by a reduction in presynaptic markers of the cholinergic system particularly in the areas of the brain related to memory and learning. In this report, we have investigated the possibility whether the processing of βAPP can be regulated by different cholinesterase inhibitors (ChE-Is), some of which have been reported to improve memory deficits and cognitive functions in some AD patients. We have recently demonstrated that the metabolism of βAPP is regulated by tacrine. Here we report a comparative study showing that the ChE-Is regulate the secretion of sAPP in a cell type-specific manner and that this effect may be independent of the anticholinesterase function.
|Original language||English (US)|
|Number of pages||6|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - Jan 1 1997|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science