Blood Based Biomarkers PIA Sid E. O’Bryant, Ph.D. Sid.obryant@unthsc.edu

Blood Based Biomarkers PIA Founding Goals of the PIA Standardization & Best Practices for the field Increasing access to data & virtual repository Establishment of validated blood biomarkers Study of blood biomarkers across neurodegenerative diseases

standardization initiative

Standardization Concerns Treatment of AD and neurodegenerative diseases is significantly hampered by the lack of easily accessible biomarkers Lack of standardization is a significant barrier to the field “unspoken rule” that <50% of academic findings replicate in industry laboratories What is the concern? Inconsistent findings in the literature Failure to replicate findings Different protocols across ongoing large-scale studies To date, largely a failure to learn from the CSF literature Becan-McBride 1999, CLSI H3-A6 – Procedures for collection of diagnostic blood: 6th ed; Henriksen et 2014; O’Bryant 2015

Effort towards standardization Recent publications from working group Henriksen, et al 2014– The Future of Blood-Based Biomarkers for Alzheimer’s Disease; Alzheimer’s & Dementia Snyder et al 2014- Developing Novel Blood-Based Biomarkers for Alzheimer’s Disease; Alzheimer’s & Dementia

Standardization Initiative in AD – preanalytic processing

Assay Issues PIA working group study Examined serum and plasma samples across platforms Data presented Thursday Symposium Session S5-01 (8:30-10am) Blood Biomarker Assays

Correlation across platforms Marker R2 p-value β2M 0.92 <0.001 IL18 0.80 FVII 0.78 CRP 0.74 FABP 0.70 sVCAM1 0.69 A2M 0.59 TNC 0.53 sICAM 0.47 I309 0.38 TNFα 0.19 0.001 THPO 0.17 0.004 PPY 0.15 0.01 IL7 0.09 0.12 IL10 0.89 Eotaxin3 IL5 -0.08 Correlation across platforms

Top AD Algorithm Markers  MSD serum   MSD Plasma RBM Serum AUC SN/SP 0.96 0.91/0.86 0.76 0.65/0.79 0.91 0.80/0.90 Rank Marker 1 IL7** Eotaxin3 Thrombopoietin 2 TNFα** PPY MIP1α 3 IL5 IL7 4 IL6 5 CRP TPO Creatine kinase 6 IL10 β2M FAS ligand 7 TNC sTNFR1 Fibrinogen 8 sICAM1 FABP 9 FVII TARC 10 I309 CA19-9 Top AD Algorithm Markers

BBB PIA Many have interest in standardization initiative Can be leveraged to assist in global standardization effort The PIA allowed for a focused effort around the topic Continuing to move forward Starting discussion of revised pre-analytic criteria now Data presented above

Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (www.dadm.alzdem.com) Partnering with PIA for special collection of articles “Latest Advances in the Science of Blood-Based Biomarkers” Guest Editor – Sid O’Bryant

Thank You