Evaluation of plasma Aβ₄₀ and Aβ₄₂ as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment

Abstract 

Numerous studies have shown a marked decrease of β-amyloid₄₂ (Aβ₄₂) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD). However, studies on Aβ in plasma are contradictory, and show very marginal differences between patients and controls. Here, we analyzed plasma samples using a new multiplex immunoassay for simultaneous analysis of Aβ_1–40, Aβ_n–40, Aβ_1–42, and Aβ_n–42. The plasma samples were obtained at baseline from two independent cohorts of patients with mild cognitive impairment (MCI) and age-matched controls. In the first cohort, 41% of the 117 MCI cases converted to AD during a clinical follow-up period of 4–7 years. In the second cohort, 14% of the 110 MCI subjects developed AD during a clinical follow-up period of 2–4 years. None of the plasma Aβ isoforms differed between MCI patients that subsequently developed AD and healthy controls or stable MCI patients. The Cox proportional hazards model did not reveal any differences in the probability of progression from MCI to AD related to plasma Aβ levels. In contrast, low levels of Aβ_1–42 in CSF were strongly associated with increased risk of future AD. The absence of a change in plasma Aβ in incipient AD, despite the marked change in CSF, may be explained by the lack of a correlation between the levels of Aβ_1–42 in CSF and plasma. In conclusion, the results show that CSF biomarkers are better predictors of progression to AD than plasma Aβ isoforms.

Keywords: Mild cognitive impairment, Alzheimer's disease, Biomarkers, Plasma, Cerebrospinal fluid, Beta-amyloid