|The amyloid protein precursor (APP) is a 110-130 kDa protein with features of an
integral transmembrane cell surface glycoprotein. APP has both N-linked and O-linked
sugars. The largest part of the molecule is the extracellular domain, which contains a
cysteine-rich region of approximately 200 amino acid residues at the N-terminus, and a
region rich in acidic residues. Some alternatively spliced mRNAs encode forms in which the
extracellular domain may contain a Kunitz protease inhibitor region and/or a domain with
homology to the OX-2 protein.
The beta-A4 (amyloid protein) sequence comprises part of the extracellular domain
and extends into the transmembrane domain of the protein. The beta-A4 sequence is cleaved
out by proteases referred to a beta and gamma secretases. These proteases have not yet
been identified. Considerable effort is being made to identify them because of the
ossibility that inhibitors of these enzymes may have therapeutic potential.