Aβ_1-17 is a major amyloid-β fragment isoform in cerebrospinal fluid and blood with possible diagnostic value in Alzheimer's disease

This work was prompted by the finding that Aβ_1-17 (Aβ₁₇) appeared to be the second-most abundant cerebrospinal fluid (CSF) Aβ fragment, after Aβ₄₀. We developed an ELISA to quantify levels of Aβ₁₇ directly accessible in plasma (DA17), recovered from the proteomic plasma matrix (RP17) and associated with the cellular pellet (CP17) that remained after plasma collection. Then, we used a sample of 19 healthy control (HC), 27 mild cognitive impairment (MCI), and 17 mild Alzheimer's disease (AD) patients to explore the association of the diagnostic groups with those direct markers, their ratios or the ratios with their Aβ₄₀ or Aβ₄₂ counterparts. After dichotomization (d) for the median of the sample population, logistic regression analysis showed that in the AD versus HC subgroup, subjects with a dDA/CP17 higher than the median had a significantly greater risk of being AD than those with marker levels equal to or below the median (odds ratio OR; 95% confidence interval; 17.21; 1.42-208.81). Subjects with dRP17/42 below the median had an increased likelihood of being MCI (20.00; 1.17-333.33) or AD (40.00; 1.87-1000) versus being HC, than those with dRP17/42 higher than the median. Although the confidence intervals are wide, these findings suggest that assessment of Aβ₁₇ may increase the diagnostic performance of blood-based Aβ tests which might be developed into minimally invasive first-step screening tests for people with increased risk for AD.