The beta APP717 Alzheimer mutation increases the percentage of plasma amyloid-beta protein ending at A beta 42(43)

We measured plasma levels of amyloid beta protein (A beta) ending at positions 40 (A beta 40) and 42(43) [A beta 42(43)] in six carriers of beta APP717 (Val to lie) mutation linked to familial Alzheimer's disease (FAD) as well as in patients with sporadic AD (sAD) and controls. The percentage and the level of A beta 42(43) were significantly higher in carriers of beta APP717 mutation relative to sAD, whereas A beta 40 levels were decreased. In contrast, A beta levels and ratios were at similar levels in sAD, regardless of the stage of the disease, compared with non-AD neurologic disease controls and nondemented control individuals, These results suggest that the reported increase in the percentage of A beta 42(43) secretion in transfected cells with beta APP717 mutant genes actually takes place in the bodies of carriers of beta APP717 mutation, and that plasma A beta could be used as an indicator of the alterations of beta APP/A beta metabolism in subtypes of AD.