ABSTRACT
This chapter will focus on what amyloid peptides do after they are made and how they may be cleared, rather than how they are produced.
Alzheimer’s Disease (AD) is characterized by a slow accumulation of aggregated central nervous system (CNS) -amyloid peptide, deposited extracellularly as amyloid fibrils in the neuropil as plaques, and in many cases, also in the vasculature. -amyloid (A) peptides of 40-43 amino acids in length (A40, A42 or A43) are a normal product derived by proteolytic processing from a larger (695-770kD) amyloid precursor protein (APP) by almost all cells, but in young individuals and many normal elderly, the peptides are successfully cleared since they fail to accumulate. A is produced by cleavage of the -APP with the N-terminal and C-terminal cuts by - and gamma-secretases, respectively. Alternatively, A production can be prevented by another endopeptidase, alpha-secretase, which cleaves within the A domain.1
