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| Name | Class |
|---|---|
| Association of Frontotemporal Degeneration | UNKNOWN |
| Tau Consortium | OTHER |
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The goal of this study is to characterize tau kinetics and tau aggregation in the human CNS and to test the hypothesis that tau kinetics are altered (i.e. increased production, decreased clearance, and increased aggregation rate) in tauopathies.
Tauopathies are neurodegenerative diseases with tau pathology. These tauopathies are the most common pathology in neurodegenerative diseases, and they are reaching epidemic proportions. The rates of tau kinetics are central to understanding normal and abnormal processing and production and clearance of tau kinetics in humans to help understand the causes of tauopathy and evaluate tau-targeted therapeutics.
This study will utilize the Stable Isotope Labeling Kinetics (SILK) method to elucidate tau kinetics in vivo in the human central nervous system (CNS) and its alteration in tauopathies. A total of ~34 participants from 3 different neurodegenerative diseases: Frontotemporal Dementia (FTD), Corticobasal Degeneration (CBD), and Progressive Supranuclear Palsy (PSP), will be invited to enroll in the study.
Participants will be labeled with stable isotopes via 16hr intravenous infusion and CSF samples collected during subsequent lumbar puncture visits over ~120 days. CSF will be analyzed over time for the quantitation of labeled tau.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Progressive Supranuclear Palsy (PSP) | N=12 Age: 18 and older Recruited participants will be given 13C6 Leucine through intravenous infusion (4mg/kg/hr for 16hrs), and CSF will be collected five times over 120 days (on approximately days 1-4, 5-10, 11-20, 21-60 and 61-120) after labeling. |
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| Corticobasal Degeneration (CBD) | N=8 Age: 18 and older Recruited participants will be given 13C6 Leucine through intravenous infusion (4mg/kg/hr for 16hrs), and CSF will be collected five times over 120 days (on approximately days 1-4, 5-10, 11-20, 21-60 and 61-120) after labeling. |
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| Frontotemporal Dementia: MAPT | N=12 Family members with or at-risk of tau mutations (e.g. P301L) Age: 18 and older Recruited participants will be given 13C6 Leucine through intravenous infusion (4mg/kg/hr for 16hrs), and CSF will be collected five times over 120 days (on approximately days 1-4, 5-10, 11-20, 21-60 and 61-120) after labeling. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 13C6 Leucine | Other | Recruited participants will be given 13C6-labeled leucine through intravenous infusion (4mg/kg/hr for 16hrs) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Tau Fractional Turnover Rate (FTR) | Calculated by using CSF tau labeling and plasma free leucine. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| CSF Tau Absolute Concentration | Measured using labeled and unlabeled tau protein isoforms that will be immunoprecipitated and analyzed by mass spectrometry. | 6 months |
| Tau Production Rate | Measured by FTR multiplied by CSF tau concentration. |
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Inclusion Criteria:
Exclusion Criteria:
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Progressive Supranuclear Palsy (PSP): N=12
Corticobasal Degeneration (CBD): N=8
Frontotemporal Dementia (FTD): MAPT: Family members with or at-risk of tau mutations (e.g. P301L) N=12
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| Name | Affiliation | Role |
|---|---|---|
| Randall Bateman, MD | Washington University in Saint Louis Medical School | Principal Investigator |
| Nupur Ghoshal, MD, PhD | Washington University in Saint Louis Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University in St. Louis School of Medicine | St Louis | Missouri | 63110 | United States |
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| ID | Term |
|---|---|
| D013494 | Supranuclear Palsy, Progressive |
| D000088282 | Corticobasal Degeneration |
| D057180 | Frontotemporal Dementia |
| D024801 | Tauopathies |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Plasma CSF
| 6 months |
| D009069 | Movement Disorders |
| D009886 | Ophthalmoplegia |
| D015835 | Ocular Motility Disorders |
| D003389 | Cranial Nerve Diseases |
| D019636 | Neurodegenerative Diseases |
| D010243 | Paralysis |
| D009461 | Neurologic Manifestations |
| D005128 | Eye Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D057174 | Frontotemporal Lobar Degeneration |
| D003704 | Dementia |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |