There is considerable interest in developing blood-based biomarkers of β-amyloid to screen individuals for the presence of significant brain β-amyloidosis, and so to focus and reduce the requirements for more expensive and/or invasive tests such as amyloid PET or lumbar puncture. Such pre-screening may be particularly valuable in asymptomatic individuals prior to entry into prevention or treatment trials. Emerging techniques for determining blood β-amyloid include immunoassays on the Single Molecule Array (Simoa) platform; and immunoprecipitation mass spectrometry (IP-MS). We compared the Simoa and IP-MS methods as pre-screening blood tests for determining β-amyloid PET positivity based on data from the Insight 46 cohort. These individuals, drawn from the MRC 1946 British Birth Cohort, were all born in mainland Britain in the same week in 1946, followed prospectively, and at age 69–71 all had detailed cognitive testing, blood sampling, 3T-MRI and 18F-Florbetapir-PET. Concentrations of Aβ1-40 and Aβ1-42 in EDTA plasma were determined using commercially available Simoa digital immunoassays (Quanterix: Aβ40 2.0 and Aβ42 2.0; 200 μL each in duplicate) and an IP-MS assay in which stable isotope-labelled recombinant Aβ peptides with known concentrations were added to 250 μL of sample, peptides were extracted using immunoprecipitation, and quantification was performed on a quadrupole-orbitrap high-resolution mass spectrometer. Plasma Aβ1-40 and Aβ1-42 biomarker data will be available for 417 cognitively normal individuals (age: 70.6±0.7yrs), of whom 77 (18.5%) were 18F-Florbetapir β-amyloid-positive (SUVR using eroded white matter reference region cut-off=0.61). Pearson correlation and Bland-Altman analyses will be used to evaluate the agreement between the Simoa and IP-MS techniques. ROC analyses adjusted for age, sex and APOE ε4 carrier status will be used to compare the utility of Aβ1-40, Aβ1-42, and Aβ1-42/40 ratio for both methods in determining amyloid-PET positivity. We will evaluate the absolute and relative reduction in amyloid-PET scan requirements that would result from using each of these methods to pre-screen cognitively normal individuals for amyloid-PET positivity. Using a large population-based cohort of cognitively normal individuals of near identical age with known PET-amyloid status provides a unique opportunity to undertake a direct comparison of two promising blood-based screening methods for quantifying β-amyloid.