?-Secretaseis an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. The transmembrane protein, contains two active site aspartate residues in its extracellular protein domain and may function as a dimer.Generation of the 40 or 42 amino acid-long amyloid-? peptides that aggregate in the brain of Alzheimer's patients requires two sequential cleavages of the amyloid precursor protein (APP). Extracellular cleavage of APP by BACE releases a soluble extracellular fragment and is followed by APP cleavage within its transmembrane domain by ?-secretase. The second cleavage releases the intracellular domain of APP and amyloid-?. Since alpha-secretase cleaves APP closer to the cell membrane than BACE does.