Plasma Amyloid and in vivo Brain Amyloid in Late Middle-Aged Hispanics

Background: Determining amyloid positivity is possible with cerebrospinal fluid and brain imaging of amyloid, but these methods are invasive and expensive. Objective: To relate plasma amyloid-beta (A beta), measured using Single-molecule array (Simoa (TM)) assays, to in vivo brain A beta, measured using positron emission tomography (PET), examine the accuracy of plasma A beta to predict brain A beta positivity, and the relation of APOE epsilon 4 with plasma A beta. Methods: We performed a cross-sectional analysis in a cohort of 345 late middle-aged Hispanic men and women (age 64 years, 72% women). Our primary plasma variable was A beta(42)/A beta(40 )ratio measured with Simoa. Brain A beta burden was measured as global SUVR with F-18-Florbetaben PET examined continuously and categorically. Results: Plasma A beta(42)/A beta 40 ratio was inversely associated with global A beta SUVR (beta = -0.13, 95% Confidence Interval (CI): -0.23, -0.03; p = 0.013) and A beta positivity (Odds Ratio: 0.59, 95% CI: 0.38, 0.91; p = 0.016), independent of demographics and APOE epsilon 4. ROC curves (AUC = 0.73, 95% CI: 0.64, 0.82; p < 0.0001) showed that the optimal threshold for plasma A beta(42)/A beta(40) ratio in relation to brain A beta positivity was 0.060 with a sensitivity of 82.4% and specificity of 62.8%. APOE epsilon 4 carriers had lower A beta(42)/A beta(40) ratio and a higher A beta positivity determined with the A beta(42)/A beta(40) ratio threshold of 0.060. Conclusion: Plasma A beta(42)/A beta(40) ratio assayed using Simoa is weakly correlated with in vivo brain amyloid and has limited accuracy in screening for amyloid positivity and for studying risk factors of brain amyloid burden when in vivo imaging is not feasible.