Elevated plasma β-amyloid peptide Aβ42 levels, incident dementia, and mortality in Down syndrome

Background: Deposition of the beta-amyloid peptide A beta(42) is thought to be an important initial step in the pathogenesis of Alzheimer disease ( AD). Individuals with Down syndrome have increased levels of beta-amyloid peptides and an increased risk for AD. Objective: To examine the relation of plasma levels of A beta(42) and A beta(40) to the risk of dementia in nondemented participants and all-cause mortality in adults with Down syndrome. Design: Prospective, community-based longitudinal cohort study. Setting: State and voluntary service providers in New York State. Participants: Adults with Down syndrome ( N=204). Main Outcome Measure: Plasma A beta(42) and A beta(40) levels were measured at initial examination. Participants were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health and vital status at 14- to 18-month intervals for 4 cycles of data collection. Results: Among participants who were nondemented at baseline, those in the middle and highest tertiles of plasma A beta(42) levels were more than 2 times as likely to develop AD as those in the lowest tertile. Compared with participants without AD, participants with prevalent AD had higher levels of plasma A beta(42) but not A beta(40). Among all participants, those in the highest tertile of plasma A beta(42) level at baseline were more than twice as likely to die during the study period as those in the lowest tertile, whereas there was no difference in risk of death between those in the middle and lowest tertiles of plasma A beta(42) level. Conclusion: Elevations in plasma A beta(42) peptide levels are associated with earlier onset of AD and increased risk of death.