P4-052: High plasma Aβ42 is a risk factor for subsequent Alzheimer's disease but a decline in Aβ42/Aβ40 ratio accompanies the onset of dementia

Abstract

Changes in plasma levels of Aβ42 and Aβ40 may be related to onset of Alzheimer's disease (AD). Plasma Aβ42 and Aβ40 were measured at initial examination and at follow-up in 892 nondemented participants in the Washington Heights-Inwood Columbia Aging Project, assessed for functional and cognitive abilities and health status at 18-month intervals. The diagnosis of dementia at follow-up was based on standard research criteria. Plasma levels of Aβ42 and Aβ40 were measured using a combination of monoclonal antibody 6E10 and rabbit antisera vs. Aβ42 and Aβ40 in a double antibody sandwich ELISA at two time points separated by approximately 4 years. Aβ42 and Aβ40 levels from the two assessment intervals were measured concurrently. We used regression analyses to estimate the risk of AD in relation to baseline Aβ42 and Aβ40 levels and the association between conversion to AD and changes in levels of Aβ peptides, Aβ42/Aβ40 ratio or by Aβ peptide change group (increasing, no change or decreasing), adjusted for covariates. At baseline, higher plasma Aβ42 levels were associated with increased risk of subsequent AD (median split HR=2.4; 95% 1.5–3.8). However, at follow-up, a decrease in Aβ42 levels, but not Aβ40 levels, was related to conversion to AD. Compared with the group with increasing levels of Aβ42, the likelihood of conversion to AD was almost 3 times higher for those whose plasma Aβ42 levels decreased over follow-up (OR=2.6, 95% CI: 1.2–5.4, p= .003), while the likelihood of AD did not differ between the group with decreasing Aβ40 and the group with increasing Aβ40 (OR= 0.6, 95% CI: 0.2–1.7). Decrease in the Aβ42/Aβ40 ratio was strongly related to conversion to AD. Those whose Aβ42/Aβ40 ratio decreased were 4 times more likely to have converted to AD over the follow-up period than those with an increasing Aβ42/Aβ40 ratio (OR= 4.2, 95% CI: 1.1–15.9). Among nondemented elders, high plasma Aβ42 is associated with increased risk of AD, while decreasing levels of plasma Aβ42 or a decline in the Aβ42/Aβ40 ratio may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aβ peptides. SUPPORT: NIA PO1-AG07232.