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Mapping the correlations between CSF Abeta and tau and hippocampal atrophy in 282 ADNI subjects

Mapping the correlations between CSF Abeta and tau and hippocampal atrophy in 282 ADNI subjects. Liana G. Apostolova, Amity E. Green, Kristy S. Hwang, Jonathan H. Morra, Jeffrey L. Cummings, Arthur W. Toga, Clifford R. Jack Jr., John Q. Trojanowski, Leslie M. Shaw,

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Mapping the correlations between CSF Abeta and tau and hippocampal atrophy in 282 ADNI subjects

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  1. Mapping the correlations between CSF Abeta and tau and hippocampal atrophy in 282 ADNI subjects Liana G. Apostolova, Amity E. Green, Kristy S. Hwang, Jonathan H. Morra, Jeffrey L. Cummings, Arthur W. Toga, Clifford R. Jack Jr., John Q. Trojanowski, Leslie M. Shaw, Michael W. Weiner, Paul Thompson

  2. Disclosures • This work was generously supported by • NIA K23 AG026803 (jointly sponsored by NIA, AFAR, The John A. Hartford Foundation, The Atlantic Philanthropies, The Starr Foundation and an anonymous donor) • UCLA ADRC NIA AG16570 • The Kassel Parkinson’s Disease and the Turken Foundations • The Easton Consortium

  3. Background • Cerebrospinal fluid (CSF) Abeta and tau are the most established and most promising fluid biomarkers in AD. • Low Abeta and increased tau levels have consistently been reported in the CSF of AD subjects as well as those MCI subjects who progress to AD. Frank RA et al., Neurobiol Aging 1998 Thal LJ et al, Alzheimer Dis Assoc Disord, 2006

  4. Background cont. • AD results in progressive hippocampal volume loss. • Hippocampal atrophy is the most established imaging biomarker in AD. • Advanced hippocampal atrophy in MCI is suggestive of underlying AD (OR for conversion to AD = 1.75) Jack, 1999 and 2004

  5. Objective: • To investigate the associations between CSF Abeta and tau levels and hippocampal atrophy in the ADNI cohort at baseline

  6. Subjects: Demographic Data Comparable to Shaw LM et al, Ann Neurol online pub

  7. CSF Biomarker Analysis • Multiplex xMAP Luminex platform • Innogenetics immunoassay kit-based reagent with the following monoclonal antibodies (Ab) • 4D7A3 Ab for Abeta • AT120 Ab for total tau • AT270 Ab for pTau181p • Day-to-day reproducibility showed less then 10% variation Shaw LM et al, Ann Neurol online pub

  8. Mean CSF Biomarker Concentrations Comparable to Shaw LM et al, Ann Neurol online pub

  9. Automated Hippocampal Segmentation AdaBoost

  10. Radial Distance Mapping

  11. Mean Hippocampal Volumes

  12. 3D Abeta1-42 correlation maps

  13. 3D Tau correlation maps

  14. 3D pTau181p correlation maps

  15. Volumetric vs. 3D radial distance associations with CSF biomarkers Hippocampal volume Hippocampal radial distance

  16. Cumulative Distribution FunctionCSF biomarker association with 3D radial distance

  17. Discussion Diagnostic accuracy of premortem CSF biomarkers Shaw LM et al, Ann Neurol online pub

  18. Summary • Hippocampal atrophy shows significant correlations with CSF biomarkers in a study sample consisting of NC, MCI and AD • 3D hippocampal surface maps show more significant associations with CSF biomarkers relative to hippocampal volumes • Abeta, Tau/Abeta1-42 and pTau181p/Abeta1-4 show the strongest correlations with 3D maps of hippocampal atrophy

  19. Future Directions • Does progressive hippocampal atrophy associate with CSF biomarker changes? • Would CSF biomarkers and hippocampal atrophy have an additive value for diagnosing early and presymptomatic AD? • Can they be combined to sensitively track disease progression and therapeutic effects?

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