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CSF tau Is it an informative biomarker of AD pathology

CSF tau Is it an informative biomarker of AD pathology. Chris Clark Alzheimer’s Disease Center University of Pennsylvania. Disclosures. T-tau and p-tau 181 ELISA kits Provided by Innogenetics. CSF tau. Increased tau predicts AD pathology at autopsy

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CSF tau Is it an informative biomarker of AD pathology

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  1. CSF tauIs it an informative biomarker of AD pathology Chris Clark Alzheimer’s Disease Center University of Pennsylvania

  2. Disclosures T-tau and p-tau 181 ELISA kits Provided by Innogenetics

  3. CSF tau • Increased tau predicts AD pathology at autopsy • tau increased when symptoms are very mild • Increased tau not present in all patients with AD

  4. Hypothesis • Effective & efficient strategy for: Diagnosis at earliest stage Evaluation of pathologically targeted treatment Monitoring treatment benefit in the community • Will be enhanced by: • Detection & monitoring of biochemical markers of AD pathology

  5. Pathology Amyloid Plaque Neurofibrillary Tangle From Lee et al. Science (1991) 251, 675-8

  6. Pathogenesis of PHF-Tau Neuron Death Neurophil Threads Tau Axon Microtubule Abnormal Phosphorylation Dendrite CSF Tau Tau PHF = PHFs Neurofibrillary Tangle Over Active Kinases Hypo-active Phosphatases Tau Senile Plaques

  7. CSF tau • Increased tau predicts AD pathology at autopsy • tau increased when symptoms are very mild • Increased tau not present in all patients with AD

  8. CSF t-tau

  9. AD vs ControlsCSF tau = 234

  10. P P P Serine 231 Threonine 231 Threonine 181 antibody tau

  11. Correlation t-tau and p-tau 181

  12. CSF tau in MCI Is CSF tau elevated early (before the onset of dementia symptoms) in the pathology of Alzheimer’s disease?

  13. CSF t-tau mildly impaired individuals(MMS >24)

  14. CSF tau in individuals with Mild Cognitive Impairment who progress to dementia

  15. Is More better than Less? Are two biomarkers better than one? • CSF tau and -amyloid • CSF tau and F2 isoprostane • Some other combination

  16. AD vs Controls AD – 19 Control - 31 F2 isoprostane >42 pg/ml AUC = 0.88

  17. Diagnostic Statistics AD (diagnosis confirmed) N = 19 Controls (clinical) N = 31

  18. Biomarker Correlations Alzheimer’s disease – pathological diagnosis N = 21

  19. CSF tau as a biochemical Marker of Alzheimer’s Disease? • Ability to detect a fundamental feature of AD neuropathology • Validated in neuropathologically confirmed AD cases • Ability to detect AD early in its course • Ability to distinguish AD from other dementias • Reliable Non-invasive, simple and inexpensive The Gold Standard

  20. CSF t-tau mildly impaired individuals(MMS >24)

  21. Annual CSF-MRI Study- 3Time points Outcome Groups NYU 2003

  22. Year 0 Year 1 Year 2 NL MCI MCI MCI NL NL Annual Group Isoprostane Differences NL n=10, MCI n=6 Subjects 8,12-iso-iPF2-VI (pg/ml) 80 = NL = MCI = MCI-AD 60 40 37 20 NYU & U of P 2003 *p<.05

  23. Classifications from Longitudinal Isoprostane Changes NL(10) MCI(6) Classification Accuracy with Sensitivity = 83% *p<.05 NYU & U of P 2003

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