1 / 26

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

piper
Download Presentation

CSF tau Is it an informative biomarker of AD pathology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related