RT Journal Article T1 Longitudinal Assessment of Tau-Associated Pathology by 18F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study. A1 Moreno-Gonzalez, Ines A1 Edwards, George A A1 Hasan, Omar A1 Gamez, Nazaret A1 Schulz, Jonathan E A1 Fernandez-Valenzuela, Juan Jose A1 Gutierrez, Antonia A1 Soto, Claudio A1 Schulz, Paul E K1 Alzheimer’s disease K1 PET imaging K1 THK5351 K1 Tau K1 biomarker K1 cognitive impairment K1 dementia K1 histological assessment K1 tauopathy K1 tracer AB Several 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. SN 2075-4418 YR 2021 FD 2021-10-12 LK https://hdl.handle.net/10668/24381 UL https://hdl.handle.net/10668/24381 LA en DS RISalud RD Apr 11, 2025