Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with more than 4.5 million Americans currently suffering from the disease. Clinical management of AD is complicated by lack of effective methods for early and accurate diagnosis of the disease. Thus, there is a significant unmet need for Alzheimer's disease diagnostic tools. The hypothesis of this project is that positron emission computed tomography (PET) imaging of pathological tau fibrils would provide an excellent biomarker for detection of tau pathology useful for both 1) Staging and monitoring progression of Alzheimer's disease and for 2) Improving early and accurate diagnosis of Alzheimer's and related tauopathies. To test this hypothesis, we will screen for and develop a novel 18F-labeled radiopharmaceutical to specifically and sensitively bind tau fibrils (the chief constituent of neurofibrillary tangles in Alzheimer's). Working with our collaborators, we have recently demonstrated a successful human proof of mechanism clinical trial for an amyloid plaque imaging agent. The tau imaging agent proposed here would provide a valuable complement to this amyloid agent by allowing for imaging of the two primary pathologies in Alzheimer's disease. Furthermore, the expertise we have developed on the amyloid project (which was also funded through SBIR grants) can now be directly applied to developing the tau specific agent. Thus Phase I of this project will now assess the feasibility of developing a tau agent by in vitro and mouse testing of multiple families of small molecules that we have developed. Phase II will test the characteristics of the biomarker proof of mechanism trials in patients under an exploratory IND. Successful accomplishment of these studies will yield an innovative radiopharmaceutical product for the evaluation and diagnosis of AD. A widely available imaging test for tau pathology in AD will yield significant scientific, commercial and societal benefits.
Public Health Relevance: Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with more than 4.5 million Americans currently suffering from the disease. Clinical management of AD and related diseases (including fronto-temporal dementia) is complicated by lack of effective methods for early and accurate diagnosis and monitoring of disease progression. Successful accomplishment of this project will provide a tau specific molecular imaging agent. When used in conjunction with amyloid specific molecular imaging agents (such as the one Avid is already developing, supported by SBIR funding) the tau specific agent would represents a significant advance towards meeting these goals for accurate diagnosis and monitoring of AD and related diseases.
Thesaurus Terms: Affinity; Aged 65 And Over; Alzheimer; Alzheimer Disease; Alzheimer Sclerosis; Alzheimer Syndrome; Alzheimer's; Alzheimer's Disease; Alzheimers Dementia; Alzheimers Disease; Amentia; American; Amyloid; Amyloid Plaques; Amyloid Substance; Area; Assay; Autoradiography; Behavioral; Beta Cell; Binding; Binding (Molecular Function); Bioassay; Biodistribution; Biologic Assays; Biological Assay; Blood - Brain Barrier Anatomy; Blood-Brain Barrier; Brain; Brain Imaging; Cat Scan, Radionuclide; Cells; Characteristics; Circumscribed Lobar Atrophy Of The Brain; Clinical Management; Clinical Trials; Clinical Trials, Unspecified; Complement; Complement Proteins; Computerized Emission Tomography; Corticodentatonigral Degeneration With Neuronal Achromasia; Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; Dementia; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Disease Progression; Disorder; Dose; Elderly; Elderly, Over 65; Emission-Computed Tomography; Encephalon; Encephalons; Evaluation; Family; Funding; Goals; Grant; Hemato-Encephalic Barrier; Human; Human, General; Idiopathic Parkinson Disease; Image; In Vitro; Insulin Cell; Insulin Secreting Cell; Label; Lewy Body Parkinson Disease; Lobar Atrophy (Brain); Mt-Bound Tau; Mammals, Mice; Man (Taxonomy); Man, Modern; Medical Imaging, Positron Emission Tomography; Methods; Mice; Mice, Transgenic; Molecular Configuration; Molecular Conformation; Molecular Interaction; Molecular Stereochemistry; Monitor; Murine; Mus; Nervous System, Brain; Neuritic Plaques; Neurodegenerative Diseases; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; Pet; Pet Scan; Pet Imaging; Petscan; Pett; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's Disease; Parkinsons Disease; Pathology; Patients; Permeability; Phase; Pick Disease Of The Brain; Pick's Disease; Positron; Positron Emission Tomography Scan; Positron-Emission Tomography; Primary Parkinsonism; Primary Senile Degenerative Dementia; Progressive Supranuclear Ophthalmoplegia; Progressive Supranuclear Palsy; Proton Magnetic Resonance Spectroscopic Imaging; Rad.-Pet; Radioautography; Radiopharmaceutical Compound; Radiopharmaceuticals; Risk; Sbir; Sbirs (R43/44); Scintigraphy, Computed Tomographic; Senile Plaques; Severity Of Illness; Small Business Innovation Research; Small Business Innovation Research Grant; Specificity; Staging; Steele-Richardson-Olszewski Disease; Steele-Richardson-Olszewski Syndrome; Supranuclear Palsy, Progressive; Tag; Tauopathies; Testing; Tomography, Emission-Computed; Toxicology; Tracer; Transgenic Mice; Treatment Efficacy; Work; Abnormally Aggregated Tau Protein; Advanced Age; Aggregation Of Microtubule Associated Protein Tau; Aggregation Of Microtubule-Associated Protein Tau; Amyloid Beta Plaque; Amyloid Imaging; Amyloid Pathology; Amyloid-B Plaque; Biomarker; Brain Visualization; Cell Imaging; Cellular Imaging; Clinical Investigation; Conformation; Conformational State; Cored Plaque; Cortico-Basal Degeneration; Corticobasal Degeneration; Dementia Of The Alzheimer Type; Diabetes; Diagnosis Evaluation; Diffuse Plaque; Disease Diagnosis; Disease Severity; Disease/Disorder; Elders; Extracellular; Filamentous Tau Inclusion; Geriatric; Hyper-Phosphorylated Tau; Hyperphosphorylated Tau; Imaging; Imaging Modality; Improved; In Vivo; Innovate; Innovation; Innovative; Intravenous Injection; Late Life; Later Life; Meetings; Microtubule Associated Protein Tau; Microtubule Associated Protein Tau Aggregation; Microtubule Associated Protein Tau Deposit; Microtubule Bound Tau; Microtubule-Associated Protein Tau; Microtubule-Associated Protein Tau Aggregation; Microtubule-Associated Protein Tau Deposit; Microtubule-Bound Tau; Mild Cognitive Disorder; Mild Cognitive Impairment; Mild Neurocognitive Disorder; Molecular Imaging; Mouse Model; Neurodegenerative Illness; Neurofibrillary Degeneration; Neurofibrillary Lesion; Neurofibrillary Pathology; Novel; Older Adult; Older Person; Paired Helical Filament; Paired Helical Filament Of Tau; Pre-Clinical; Preclinical; Primary Degenerative Dementia; Public Health Relevance; Radioactive Drugs; Radionuclide Emission Tomography; Response; Self-Aggregate Tau; Senile Dementia Of The Alzheimer Type; Senior Citizen; Small Molecule; Tangle; Tau; Tau Phf; Tau Phf Formation; Tau Proteins; Tau Accumulation; Tau Aggregate; Tau Aggregation; Tau Associated Neurodegeneration; Tau Associated Neurodegenerative Process; Tau Factor; Tau Fibrillization; Tau Filament; Tau Filament Assembly; Tau Induced Neurodegeneration; Tau Mediated Neurodegeneration; Tau Neurodegenerative Disease; Tau Neurofibrillary Tangle; Tau Neuropathology; Tau Oligomer; Tau Paired Helical Filament; Tau Paired Helical Filament Formation; Tau Polymerization; Tau Self-Aggregate; Tau-Tau Interaction; Tauopathic Neurodegenerative Disorder; Tauopathy; Therapeutic Efficacy; Therapeutically Effective; Tool
