1. Notes of 21nov2011 Alz. Assoc. CSF Reference Method Sub-group

2. Goal Quantify concentration of analyte as accurately as possible in the reference material to then be used to compare other methods and platforms available…

3. Methods to evaluate (for pros/cons) MRM published by Waters et al… (need cite) Absorbance based methods PPD (Randy Jenkins)- Assay from ICAD poster Proteome Sciences - “validated” ab42 assay C2N – quant ab42 and “total ab” assay Immunoassay based approaches – MSD, Myriad RBM, INNX/Fujirebio Manu Vandijeck had a new methodogy from Ab42 std working group… Note: need request validation reports from each.

4. Reference Methods Issues Issue: are we considering what is available today or what may need to get developed Consideration of pre-analytic methods and their impact on the analytical methods Oligomer vs monomer of Ab42 What is the minimum validation required? What is the quality standard? What is overall target goal? FDA clearance or approval, operate in research space only? Resources to achieve the goals? Suggest pull EMA opinions based on BMS submission regarding CSF biomarkers MSD-RUO initially, require more than MSD alone if tied to drug or indication, working on how take to next level, what are clinical study design and samples for a PMA... Invite DX companies: OCD, Roche to the “table”, CRO have done “validated” Pfizer/ICON, Issue: is method/assay validated and available? Where should it be done?