Elevated plasma amyloid β-peptide 1-42 and onset of dementia in adults with Down syndrome

We compared levels of plasma amyloid β-peptides Aβ1-42 and Aβ1-40 in 108 demented and nondemented adults with Down syndrome (DS) and 64 adults from the general population. Aβ1-42 and Aβ1-40 levels were significantly higher in adults with DS than in controls (P = 0.0001). Compared to nondemented adults with DS, Aβ1-42 levels in demented adults with DS were selectively increased by 26% (28.2 pg/ml vs. 22.4 pg/ml, P = 0.004). In addition, mean plasma levels of Aβ1-42 were 22% higher in DS cases with the apolipoprotein ε4 allele than in DS subjects without an ε4 allele (25.9 pg/ml vs. 21.2 pg/ml, P = 0.01), while mean plasma levels of Aβ1-40 did not vary by APOE genotype. These results support the hypothesis that Aβ1-42 plays an important role in the pathogenesis of dementia associated with DS, as it does in Alzheimer's disease, and that variations in plasma levels may be related to disease progression.