The A4 amyloid protein is the major subunit present in the amyloid of Alzheimer's disease. It is derived by proteolytic cleavage from a larger precursor (PreA4) which is a neuronal membrane glycoprotein. Whereas in Down's syndrome, over-expression of the gene coding for PreA4 is likely to be responsible for the premature development of cerebral amyloidosis, a similar mechanism is yet to be demonstrated in Alzheimer's disease.