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P1–171: A new era of CSF biomarker testing in the field of Alzheimer's disease

2013; Wiley; Volume: 9; Issue: 4S_Part_5 Linguagem: Inglês

10.1016/j.jalz.2013.05.394

1552-5279

Sebastiaan Engelborghs, Erik Stoops, Britta Brix, Leentje Demeyer, Dirk Jacobs, Hanne Struyfs, Eugeen Vanmechelen,

Electrochemical sensors and biosensors

In the field of Alzheimer's disease (AD) diagnostics and clinical trials, there is an urgent need to establish novel concepts for CSF biomarker testing. These novel concepts should allow earlier identification of specific brain pathology (e.g., amyloidopathy, tauopathy, loss of synapses) and should help predict the progression rate in disease-affected subjects. Last but not least, approval of the assays for inclusion in clinical trials is indispensable. Notwithstanding the proven clinical utility of the CSF biomarkers, such as phosphorylated tau or the β-Amyloid (Aβ) proteins, all currently available immunoassays lack important analytical performance characteristics, hampering their world-wide integration and approval by regulatory authorities, especially in the US. The present study describes solutions for these analytical drawbacks. In addition, the qualification of the clinical utility of integrating CSF- Aβ(1–40) in the panel as an aid for differential dementia diagnosis, was performed. The analytical and clinical qualification of the newly developed assay studies was performed using well-characterized CSF samples from multiple expert centers and carefully designed study protocols. The subject population included controls, patients with AD or vascular dementia (VAD). The outcome of the current assays was compared on-site with and using the same sample set to commercially available single analyte immunoassay formats. Extensive qualification data for raw materials and assay characteristics will be presented, including but not limited to the selected monoclonal antibodies (e.g., precision, sensitivity, matrix interference, accuracy, run acceptance, stability). The formulation of the reagents included in the assay as well as the assay design resulted in the absence of matrix interference. The automation and the availability of ready-to-use calibrators with good stability further adds to the robustness of the approach. The newly qualified assays for m-Tau and Aβ(1–42), combined with assays for Aβ(1–40), allow for a more reliable quantification in CSF, ultimately resulting in a better clinical diagnostic accuracy and improved patient selection for clinical trials. The sharing of performance characteristics of our novel approaches will be beneficial for the whole AD community.