Moreno-Gonzalez, InesEdwards III, George A.Hasan, OmarGamez, NazaretSchulz, Jonathan E.Fernandez-Valenzuela, Juan JoseGutierrez, AntoniaSoto, ClaudioSchulz, Paul E.2022-12-122022-12-122021-10-12Moreno-Gonzalez I, Edwards GA III, Hasan O, Gamez N, Schulz JE, Fernandez-Valenzuela JJ, et al. Longitudinal Assessment of Tau-Associated Pathology by 18F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study. Diagnostics. 2021 Oct 12;11(10):1874http://hdl.handle.net/10668/4483Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer's disease (AD), NFTs are accompanied by extracellular amyloid-beta (Aβ), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. 18F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer 18F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo 18F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that 18F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/PET imagingTauTHK5351TracerBiomarkerHistological assessmentCognitive impairmentTauopathyAlzheimer’s diseaseDementiaTomografía por emisión de positronesProteínas tauTrazadores radiactivosBiomarcadoresTécnicas histológicasDisfunción cognitivaTauopatíasEnfermedad de AlzheimerDemenciaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Dementia::Alzheimer DiseaseMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Dementia::Frontotemporal Lobar Degeneration::Frontotemporal DementiaMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::GliosisMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Neurofibrils::Neurofibrillary TanglesMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Supranuclear Palsy, ProgressiveMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Cytoskeletal Proteins::Microtubule Proteins::Microtubule-Associated Proteins::tau ProteinsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Image Interpretation, Computer-Assisted::Tomography, Emission-Computed::Positron-Emission TomographyMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Tomography, Emission-Computed::Positron-Emission TomographyMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Isotopes::Radioisotopes::Radioactive TracersMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Dementiaresearch article34679572Acceso abierto10.3390/diagnostics111018742075-4418PMC8535097