A blind trial of Aptamarker prediction of brain amyloid based on plasma analysis

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Abstract We previously described the development of a predictive blood test for brain amyloid based on the combined use of eight aptamers (Aptamarkers) and the clinical variable, patient age with a sensitivity of 88%, specificity of 76% and an overall accuracy of 81%. This test results from an agnostic application of a defined library of 4.29 billion aptamer sequences to plasma samples derived from individuals with varying amounts of brain amyloid deposition. In this report, the same eight Aptamarkers and corresponding predictive algorithm were applied to plasma samples from 36 patients diagnosed with memory impairment in a memory clinic in Portugal. The patients were all subjected to cerebrospinal fluid (CSF) analysis with Aβ40, Aβ4 peptides, p181-tau and total tau characterization. The plasma analysis with the Aptamarkers resulted in a sensitivity of 73%, specificity of 71% and overall accuracy of 72% when considering brain amyloid alone. The predictive power when considering the diagnosis of Alzheimer’s disease based on a complete CSF analysis was a sensitivity of 68%, a specificity of 76% and an overall accuracy of 72%. These results in this diagnostic accuracy study are very similar to results obtained with model building on AIBL cohort. As such, this study demonstrates the potential efficacy of this simple qPCR assay as a basis for inclusion for subsequent CSF confirmation of brain amyloid deposition in a clinical setting.

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