Biospecimen Data Brit Mollenhauer Douglas Galasko Lesley Shaw - PowerPoint PPT Presentation

Biospecimen Data • Brit Mollenhauer • Douglas Galasko • Lesley Shaw • John Trojanowski

• 1. Longitudinal CSF analysis ongoing • 2. Reanalysis plan with completed 2 year follow-up • 3. Suggestions for exploratory studies with BIOFIND/ PPMI samples

1.1 Longitudinal CSF at Baseline, 6 Months, and 12 Months reveals slight changes

1.2 Predictors of change for CSF proteins at 12 months in PD (mutlivariate regression) CSF Abeta 42 CSF t-tau CSF p-tau Univari # Multiva Multiv Univariat # Multivari Multiva Univari # Multiva Multiv ate Observa riate ariate e Observati ate riate ate Observa riate ariate tions ons tions Variable p-value Missing Estimat p- Variable p-value Missing Estimate p-value Variable p-value Missing Estimat p- e value Age at Baseline LP 0.5459 0 - - e value Age at Baseline 0.5970 0 - - Age at Baseline LP 0.8551 0 - - Gender 0.6015 0 - - LP Gender 0.0008 0 -90.40 0.0006 Age at PD Onset 0.5502 4 - - Gender 0.3835 0 - - Age at PD Onset 0.5339 4 - - Age at PD Onset 0.4565 4 - - MDS-UPDRS Total 0.4950 0 - - MDS-UPDRS Total 0.3648 0 - - MDS-UPDRS Total 0.1791 0 - N.S. Score Score Score MDS-UPDRS Part III 0.7738 0 - - MDS-UPDRS Part 0.2005 0 - - MDS-UPDRS Part 0.4761 0 - - (Motor) Sco III (Motor) Sco III (Motor) Sco TD/non-TD 0.9369 0 - - TD/non-TD 0.2033 0 - - TD/non-TD 0.6403 0 - - Classification Classification Classification HVLT Total Recall 0.5252 0 - - HVLT Total Recall 0.6906 0 - - HVLT Total Recall 0.4291 0 - - HVLT Delayed 0.1611 0 - N.S. HVLT Delayed Recall 0.6377 0 - - HVLT Delayed 0.7635 0 - - Recall Recall HVLT Discrimination 0.2876 0 - - HVLT 0.2450 0 - - HVLT 0.8465 0 - - Recognitio Discrimination Discrimination MOCA 0.2192 0 - - Recognitio Recognitio MOCA 0.1669 0 - N.S. MOCA 0.3871 0 - - SDM 0.4132 0 - - SDM 0.5915 0 - - SDM 0.3839 0 - - LNS 0.0294 0 13.26 0.0093 LNS 0.1297 0 - N.S. LNS 0.9383 0 - - BJLO 0.4324 0 - - BJLO 0.1066 0 12.62 0.0254 BJLO 0.8258 0 - - ApoE e4 0.7377 4 - - ApoE e4 0.3791 4 - - ApoE e4 0.4349 4 - - SNCA rs3910105 0.0095 13 -41.78 0.0114 SNCA rs3910105 0.1205 13 - N.S. SNCA rs3910105 0.2984 13 - - SNCA rs356181 0.0150 13 - N.S. SNCA rs356181 0.1320 13 - N.S. SNCA rs356181 0.0187 13 35.88 0.0236 MAPT 0.9572 13 - - MAPT 0.8683 13 - - MAPT 0.2925 13 - - Mean Caudate 0.8949 0 - - Mean Caudate 0.7197 0 - - Mean Caudate 0.6139 0 - - Mean Putamen 0.6344 0 - - Mean Putamen 0.2837 0 - - Mean Striatum 0.7920 0 - - Mean Putamen 0.6131 0 - - Mean Striatum 0.8958 0 - - Mean Striatum 0.5911 0 - -

1.3 Correlation analysis with between CSF marker changes and MDS-UPDRS revealed significant correlation of CSF aSyn with MDS- UPDRS total score to 6- and 12-months in PD.

2. Longitudinal CSF Re-analysis Plan as of Fall 2014 • Analysis of ONE aliquot (0.5 ml) CSF BL, 6 month, 12 and 24 month visit (n= 2014) • (1) For CSF tau, Abeta, phospho-tau by UPenn (Alzbio3 or alternative automated platform) • Rest aliquot send to BioLegend, Mesoscale (or alternative) • (2) For CSF alpha-synuclein

PPMI samples available to date

Proposed Timeline • Finalize longitudinal data manuscript • Wait for finalisation of 24 month follow-up (May/ June 2015) after the new repository established and assays finalized • Analysis all samples side-by-side September/ October 2015 (considering an automated platform)

ALPHA-SYNUCLEIN ASSAY STANDARDIZATION LEAPS 2014 Mass- Assays: spec (3 platforms) J. Zhang H. Zetterberg Comparison of Covance MSD and Mollenhauer MSD (PNNL) /BioLegen (Luminex) Singleplex (ISB) ELISA 1. Covance/BioLegend 1. MSD/Umek 1. J. Zhang /Taylor 2. B. Mollenhauer 2. B. Mollenhauer 2. B. Mollenhauer 3. H. Zetterberg 3. H. Zetterberg 3. H. Zetterberg satellites Samples: 4. J. Zhang 4. J. Zhang J. Zhang CSF, 5. O. El-Agnaf saliva, whole blood To be used in 3 Standard/ assay platforms MJFF/ calibrator and verified by TBD B. Mollenhauer production mass-spec 9

3. Suggestions for exploratory studies with BIOFIND/ PPMI samples • New marker candidates for progression are needed

Discovery projects - NINDS Parkinson's Disease Biomarkers Program (PDBP) - MJFF funded discovery projects, antibody activities (DJ-1 etc.) - Pathway/ Genetically based - Suggestion: one-day Biomarker Discovery Workshop

• NEXT STEPS/ DISCUSSION POINTS • Further development of assays focusing on different forms of synuclein (PTMS, oligomers) • Targeted/ untargeted -omic discovery (Caprion/ Soamlogic/ Metabolomic) • Pathwayy/ Genetically driven Clemens Scherzer/ Judy Potashkin Prepare for LRRK-2 and GBA analyses