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Biomarkers of Alzheimer’s Disease

Biomarkers of Alzheimer’s Disease. Purpose. Biomarkers of Alzheimer’s Disease. Objectively mark Presence of neurodegenerative pathology Change in pathologic activity. Advantages. Biomarkers of Alzheimer’s Disease. Early detection of neurodegenerative pathology.

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Biomarkers of Alzheimer’s Disease

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  1. Biomarkers of Alzheimer’s Disease

  2. Purpose Biomarkers of Alzheimer’s Disease Objectively mark • Presence of neurodegenerative pathology • Change in pathologic activity

  3. Advantages Biomarkers of Alzheimer’s Disease • Early detection of neurodegenerative pathology • Improve diagnostic certainty in challenging patients • Increased diagnostic accuracy by non-specialist • Increased diagnostic efficiency(time & Money) • Objective monitoring of treatment efficacy

  4. Biomarkers of AD MRI Anatomical • Regional volume – cross sectional & longitudinal • Boundary shift – longitudinal Macromolecular • T1 rho • Magnetization transfer Biochemical • MR spectroscopy Physiologic • Function induced regional changes in blood flow

  5. Biomarkers of AD PET Regional metabolic impairment • Standard format • Stereotaxtic Surface Projection Pathology specific imaging • Amyloid ligand imaging

  6. Biomarkers of AD Biochemical • Tau • Amyloid • Isoprostane • Sulfatide • Proteomics

  7. Based on tau pathology, neuron loss, gliosis 3R-tau 3R/4R-tau 4R-tau 1. NFT dementia 2.FTDP-17 3. Other 4. AD 1. CBD 2. PSP 3. FTDP-17 4. Other 1. Pick’s disease 2. FTDP-17 3. Other Frontotemporal DementiaNeuropathological Classification Courtesy of John Trojanowski

  8. Altered proteins in CSF of AD patients Mw (kDa) 70 45 40 30 15 8 pH 4-7 Circles= reduced protein intensity (p<0.001) Squares = increased protien intensity (p<0.001) Courtesy Pia Davidsson 2003

  9. Molecular and Biochemical Markers 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 Neurobiology of Aging 19:109-116, 1998

  10. Biomarkers of Alzheimer’s Disease Criteria to identify and validate – Richard Mayeux Biomarkers old and new • CSF tau – Chris Clark • CSF amyloid – Doug Galasko • CSF sulfatide – Dave Holtzman • F2 isoprostane – Domenico Pratico • Neuroimaging – Mike Weiner Panel discussion

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