O2–06–02: Plasma Aβ_1–40 and Aβ_1–42 and the risk of dementia

Abstract

Amyloid β–peptides (Aβ), Aβ1–40and Aβ1–42, are important components of senile plaques, hallmarks of Alzheimer's disease. Plasma levels of Aβ1–40 and Aβ1–42 increase with age and are increased in persons that carry mutations that cause early onset Alzheimer's disease. It has been suggested that plasma Aβ1–42 decreases early in the dementia process. We hypothesized an association of high levels of plasma Aβ1–40 and concomitant low levels of Aβ1–42 with an increased risk of dementia. We investigated the association between plasma Aβ and risk of dementia. We investigated this association in a case–cohort study embedded in the prospective, population–based Rotterdam Study. Of 6,713 participants at risk for dementia, a random sample of 1,756 persons was drawn. During follow–up (mean 8.6 years) 162 incident dementia cases were identified in this random sample. We added 230 dementia patients who developed dementia during follow–up outside the random sample. Cox' proportional hazard models with modification of standard errors were used to estimate the association of plasma Aβ levels and risk of dementia. High plasma levels of Aβ1–40 but not Aβ1–42 were associated with an increased risk of dementia. Compared to the first quartile of Aβ1–40, age and sex adjusted hazard ratios (95% confidence interval) for dementia for the second, third and fourth quartiles were 1.07 (0.72–1.58), 1.16 (0.78–1.70) and 1.46 (1.01–2.12) (p–value for trend 0.03). Persons with an increased Aβ1–42/Aβ1–40 ratio had a lower risk of dementia. Compared to the first quartile of the Aβ1–42/Aβ1–40 ratio, age and sex adjusted hazard ratios (95% confidence interval) for dementia for the second, third and fourth quartiles were 0.74 (0.51–1.08), 0.68 (0.46–1.01) and 0.53 (0.35–0.81) (p–value for trend 0.003). Additional adjustment for creatinine and cardiovascular factors did not change the associations. The associations were not different in carriers and non–carriers of the APOE ϵ4 allele. Persons with high Aβ1–40 especially when combined with low plasma Aβ1–42 have an increased risk of dementia. These findings suggest that plasma Aβ levels may be of use in the prediction of dementia.