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Translational Imaging Strategies for Therapeutic Discovery in Alzheimer Disease

Translational Imaging Strategies for Therapeutic Discovery in Alzheimer Disease. Jeffrey R. Petrella , MD Associate Professor of Radiology Duke University Health System. Alzheimer’s Disease. Plaques. Tangles. Alois Alzheimer (1864-1915). Cell damage Cell death. Pathophysiology of AD.

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Translational Imaging Strategies for Therapeutic Discovery in Alzheimer Disease

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  1. Translational Imaging Strategies for Therapeutic Discovery in Alzheimer Disease Jeffrey R. Petrella, MD Associate Professor of Radiology Duke University Health System

  2. Alzheimer’s Disease Plaques Tangles Alois Alzheimer (1864-1915)

  3. Cell damageCell death Pathophysiology of AD Genetic Amyloid Inflammation Risk Tangles Oxidation Symptoms Birth 60 100 Years Adapted from Doraiswamy 2000, Sunderland 1999

  4. Blood oxygenation level Functional MRI - principles Blood flow Metabolism Function

  5. Hippocampal Activation @ 4T Encode: novel vs familiar

  6. Control 3 MCI y = -0.1002x + 0.5029 2 AD 2 R = 0.2524 1 0 -1 -2 -1 4 9 14 19 Signal Intensity (Petrella et al, Radiology, 2007) CVLT-II delayed recall score

  7. Activation Parameter Estimate Activation Parameter Estimate PMC region of interest (Petrella, et al., PLoS ONE Oct 2007)

  8. Default Mode Network Control MCI-S MCI-C Petrella et al., Neurology 2011

  9. Measuring treatment effects with fMRI Baseline Scan A. Petrella et al., AJNR 2009 Post-Treatment Follow-up Scan Placebo group Donepezil group B. C.

  10. Cell damageCell death Use Biomarker paired to drug mechanism Genetic Amyloid Inflammation Risk Tangles Oxidation Neuropsychologic Testing CSF, Blood Biomarkers MR Perfusion fMRI DTI Symptoms Birth 60 100 Molecular Imaging FDG- PET MR Spectro-scopy Quantitative/ Structural MR Years Reproduced from Doraiswamy 2000, Sunderland 1999

  11. Alzheimer Disease International, World Alzheimer Report 2010

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