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

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

Nov 28, 2023 482 likes •614 views

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

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SLIDE 1
  • Brit Mollenhauer
  • Douglas Galasko
  • Lesley Shaw
  • John Trojanowski

Biospecimen Data

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SLIDE 2
  • 1. Longitudinal CSF analysis ongoing
  • 2. Reanalysis plan with completed 2

year follow-up

  • 3. Suggestions for exploratory

studies with BIOFIND/ PPMI samples

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SLIDE 3

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

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SLIDE 4

1.2 Predictors of change for CSF proteins at 12 months in PD (mutlivariate regression)

Univari ate # Observa tions Multiva riate Multiv ariate Variable p-value Missing Estimat e p- value Age at Baseline LP 0.5970

  • Gender

0.3835

  • Age at PD Onset

0.4565 4

  • MDS-UPDRS Total

Score 0.1791

  • N.S.

MDS-UPDRS Part III (Motor) Sco 0.4761

  • TD/non-TD

Classification 0.6403

  • HVLT Total Recall

0.4291

  • HVLT Delayed

Recall 0.7635

  • HVLT

Discrimination Recognitio 0.8465

  • MOCA

0.3871

  • SDM

0.3839

  • LNS

0.1297

  • N.S.

BJLO 0.1066 12.62 0.0254 ApoE e4 0.3791 4

  • SNCA rs3910105

0.0095 13

  • 41.78

0.0114 SNCA rs356181 0.0150 13

  • N.S.

MAPT 0.9572 13

  • Mean Caudate

0.8949

  • Mean Putamen

0.6344

  • Mean Striatum

0.7920

  • CSF Abeta 42

Univari ate # Observa tions Multiva riate Multiv ariate Variable p-value Missing Estimat e p- value Age at Baseline LP 0.8551

  • Gender

0.0008

  • 90.40

0.0006 Age at PD Onset 0.5339 4

  • MDS-UPDRS Total

Score 0.3648

  • MDS-UPDRS Part

III (Motor) Sco 0.2005

  • TD/non-TD

Classification 0.2033

  • HVLT Total Recall

0.6906

  • HVLT Delayed

Recall 0.1611

  • N.S.

HVLT Discrimination Recognitio 0.2450

  • MOCA

0.1669

  • N.S.

SDM 0.5915

  • LNS

0.9383

  • BJLO

0.8258

  • ApoE e4

0.4349 4

  • SNCA rs3910105

0.2984 13

  • SNCA rs356181

0.0187 13 35.88 0.0236 MAPT 0.8683 13

  • Mean Caudate

0.7197

  • Mean Putamen

0.2837

  • Mean Striatum

0.8958

  • CSF p-tau

Univariat e # Observati

  • ns

Multivari ate Multiva riate Variable p-value Missing Estimate p-value Age at Baseline LP 0.5459

  • Gender

0.6015

  • Age at PD Onset

0.5502 4

  • MDS-UPDRS Total

Score 0.4950

  • MDS-UPDRS Part III

(Motor) Sco 0.7738

  • TD/non-TD

Classification 0.9369

  • HVLT Total Recall

0.5252

  • HVLT Delayed Recall

0.6377

  • HVLT Discrimination

Recognitio 0.2876

  • MOCA

0.2192

  • SDM

0.4132

  • LNS

0.0294 13.26 0.0093 BJLO 0.4324

  • ApoE e4

0.7377 4

  • SNCA rs3910105

0.1205 13

  • N.S.

SNCA rs356181 0.1320 13

  • N.S.

MAPT 0.2925 13

  • Mean Caudate

0.6139

  • Mean Putamen

0.6131

  • Mean Striatum

0.5911

  • CSF t-tau
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SLIDE 5

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.

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SLIDE 6
  • 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
  • 2. Longitudinal CSF Re-analysis Plan

as of Fall 2014

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SLIDE 7

PPMI samples available to date

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SLIDE 8

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)

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SLIDE 9

9

ALPHA-SYNUCLEIN ASSAY STANDARDIZATION LEAPS 2014

Mass- spec Assays:

(3 platforms)

Samples:

CSF, saliva, whole blood

  • J. Zhang
  • H. Zetterberg

(PNNL) (ISB)

  • J. Zhang
  • B. Mollenhauer

Covance /BioLegen ELISA (Luminex) MSD

  • 1. MSD/Umek
  • 2. B. Mollenhauer
  • 3. H. Zetterberg
  • 4. J. Zhang

Comparison of MSD and Mollenhauer Singleplex

satellites

  • 1. J. Zhang
  • 2. B. Mollenhauer
  • 3. H. Zetterberg
  • 1. Covance/BioLegend

/Taylor

  • 2. B. Mollenhauer
  • 3. H. Zetterberg
  • 4. J. Zhang
  • 5. O. El-Agnaf

Standard/ calibrator production

MJFF/ TBD To be used in 3 assay platforms and verified by mass-spec

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SLIDE 10
  • 3. Suggestions for exploratory studies

with BIOFIND/ PPMI samples

  • New marker candidates for

progression are needed

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SLIDE 11

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

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SLIDE 12
  • NEXT STEPS/ DISCUSSION POINTS
  • Further development of assays focusing
  • n 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