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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
CSF tauIs it an informative biomarker of AD pathology

Chris Clark

Alzheimer’s Disease Center

University of Pennsylvania

disclosures

Disclosures

T-tau and p-tau 181 ELISA kits

Provided by Innogenetics

csf tau
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
hypothesis
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
slide5

Pathology

Amyloid Plaque

Neurofibrillary Tangle

From Lee et al. Science (1991) 251, 675-8

pathogenesis of phf tau
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

csf tau7
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
slide12

P

P

P

Serine

231

Threonine

231

Threonine

181

antibody

tau

correlation
Correlation

t-tau and p-tau 181

slide15

CSF tau in MCI

Is CSF tau elevated early (before the onset of dementia symptoms) in the pathology of Alzheimer’s disease?
is more better than less
Is More better than Less?

Are two biomarkers better than one?

  • CSF tau and -amyloid
  • CSF tau and F2 isoprostane
  • Some other combination
ad vs controls
AD vs Controls

AD – 19

Control - 31

F2 isoprostane >42 pg/ml

AUC = 0.88

diagnostic statistics
Diagnostic Statistics

AD (diagnosis confirmed) N = 19

Controls (clinical) N = 31

biomarker correlations
Biomarker Correlations

Alzheimer’s disease – pathological diagnosis

N = 21

csf tau as a biochemical marker of alzheimer s disease
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

slide25

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

slide26

Classifications from Longitudinal Isoprostane Changes

NL(10) MCI(6)

Classification Accuracy with Sensitivity = 83%

*p<.05

NYU & U of P 2003