Beta- Amyloid Peptides
ß-Amyloid (Aß) peptides are generated as cleavage products 39 to 43 amino acids in length from the membrane protein,Amyloid Precursor Protein (APP) by two proteases, ß-secretase and ã-secretase (1-3). While only a small amount is processed by â-Secretase, also known as BACE1 (â-secretase APP cleaving enzyme) or memapsin, APP is predominantly processed by á-Secretase, producing a 83-amino acid C-terminal fragment, C83. Subsequent cleavage of C83 by ã-secretase produces a non-toxic N-terminal 3kD protein (1-2).
Aßs are amphiphilic peptides with a hydrophilic N-terminal domain (residues 1 to 28) and a hydrophobic C-terminal (residues 29 to 40-42), the latter corresponding to a part of the transmembrane domain of APP (4). ß-Amyloid assembly into fibrils is initiated by a conformational transition from random coil to ß-sheet (hence the name ß-amyloid) and a nucleation-dependent aggregation process (4). Aß peptides that are 39 to 42 amino acid residues in length with a molecular mass of approximately 4 kDa are the core components of neuritic plaques seen in Alzheimer's disease (AD) brains. The presence of excess amount of Aß deposits and neurofibrillary tangles, NFTs (5-6), comprising of hyperphosphorylated Tau proteins are the hallmarks of an AD brain (1).