ADC Fall An update on biomarkers in AD and non-ad dementias

Transcription

1 ADC Fall 2010 An update on biomarkers in AD and non-ad dementias Thomas J. Montine, MD, PhD Alvord Chair of Neuropathology Professor of Pathology and Neurological Surgery University of Washington Adjunct Professor of Neurology Oregon Health & Science University

2 Stages of s to be met by biomarkers and molecular neuroimaging Laboratory Determine degree and character of functional impairment Normal Mild Impairment Moderate to Severe Impair. Classify disease type and burden of lesions None Stage No Latency Prodrome Dementia

3 Stages of s to be met by biomarkers and molecular neuroimaging Laboratory Determine degree and character of functional impairment Normal Mild Impairment Moderate to Severe Impair. Classify disease type and burden of lesions None Stage No Latency Prodrome Dementia

4 Stages of s to be met by biomarkers and molecular neuroimaging Laboratory Determine degree and character of functional impairment Normal Mild Impairment Moderate to Severe Impair. Classify disease type and burden of lesions None Stage No Latency Prodrome Dementia

5 Stages of s to be met by biomarkers and molecular neuroimaging Neuropath Imaging Biomarkers Stage Determine degree and character of functional impairment Normal Mild Impairment AD, LBD, and µvbi Moderate to Severe Impair. None No Identify diseasespecific latency Latency Prodrome Dementia Quantify disease-specific progression Quantify pharmacologic activity of experimental therapeutics

6 Stages of s to be met by biomarkers and molecular neuroimaging Neuropath Imaging Biomarkers Stage Determine degree and character of functional impairment Normal Mild Impairment AD, LBD, and µvbi Moderate to Severe Impair. None No Latency Prodrome Dementia Identify disease-specific latency and prodrome Quantify disease progression Quantify pharmacologic activity of experimental therapeutics

7 Quality of evidence Compartment Level 1 Initial Associations Association with expert diagnosis Level 2 Confirmation Replication in independent sample that includes multiple related diseases Level 3 Validation Further replication in independent samples from multiple sites Level 4 Research Standardization of assay and use as disease surrogate in clinical research Level 5 Primary Care Adopted as part of standard work-up in primary care setting

8 Quality of evidence Compartment

9 Quality of evidence Compartment CSF continues to be the site to yield reproducible results for diseases that cause cognitive impairment and dementia.

10 CSF biomarkers for AD CSF biomarkers of drug action CSF biomarkers for cognitive impairment in PD Evidence Latency Prodrome Dementia Level 1 Level 2 Level 3 Level 4 Level 5 Several F 2 -IsoPs tau-p231 Aβ 42, T-tau, tau-p181 None Many candidates F 2 -IsoPs, BACE1 tau-231 Aβ 42 and T-tau tau-p181 Many candidates A few MAPs tau-p231 F 2 -IsoPs Aβ 42, T-tau, tau-p181 None None None

11 CSF biomarkers for AD CSF biomarkers of drug action CSF biomarkers for cognitive impairment in PD Evidence Latency Prodrome Dementia Level 1 Level 2 Level 3 Level 4 Level 5 Several F 2 -IsoPs tau-p231 Aβ 42, T-tau, tau-p181 None Many candidates F 2 -IsoPs, BACE1 tau-231 Aβ 42 and T-tau tau-p181 Many candidates A few MAPs tau-p231 F 2 -IsoPs Aβ 42, T-tau, tau-p181 None None None

12 CSF biomarkers for AD CSF biomarkers of drug action CSF biomarkers for cognitive impairment in PD

13 CSF biomarkers for AD CSF biomarkers of drug action CSF biomarkers for cognitive impairment in PD

14 Summary Neuropath Imaging Biomarkers Stage Determine degree and character of functional impairment Normal Mild Impairment AD, LBD, and µvbi Moderate to Severe Impair. None No Latency Prodrome Dementia Identify disease-specific latency and prodrome Quantify disease progression Quantify pharmacologic activity of experimental therapeutics

15 Summary CSF Aβ42 and tau species for AD CSF Aβ42 for PD Neuropath Imaging Biomarkers Stage Determine degree and character of functional impairment Normal Mild Impairment AD, LBD, and µvbi Moderate to Severe Impair. None No Latency Prodrome Dementia Identify disease-specific latency and prodrome Quantify disease progression Quantify pharmacologic activity of experimental therapeutics

16 Summary CSF Aβ42 and tau species for AD CSF Aβ42 for PD Neuropath Imaging Biomarkers Stage Determine degree and character of functional impairment Normal Mild Impairment? CSF tau and others AD, LBD, and µvbi Moderate to Severe Impair. None No Latency Prodrome Dementia Identify disease-specific latency and prodrome Quantify disease progression Quantify pharmacologic activity of experimental therapeutics

17 Summary CSF Aβ42 and tau species for AD CSF Aβ42 for PD Neuropath Imaging Biomarkers Stage Determine degree and character of functional impairment Normal Mild Impairment? CSF tau and others AD, LBD, and µvbi Moderate to Severe Impair. None No CSF Aβ42 production for GSIs CSF F 2 -IsoPs for anti-oxidants Latency Prodrome Dementia Identify disease-specific latency and prodrome Quantify disease progression Quantify pharmacologic activity of experimental therapeutics

18 Future Directions Patient Evaluation Medical history and genetics to quantify risk examination and neuropsych testing Laboratory: Ensemble of imaging and biomarker data Aid in diagnosis Establish disease stage Quantify progression or response to therapy Research needs Reproducible peripheral biomarkers Focus on latent and prodromal stages Demonstrate pharmacologic action prior to therapeutic trial

19 Thanks to Patients and their families Members of UW ADRC Alvord Endowment NIH for support