Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study
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...
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MDPI AG
2021-10-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/11/10/1874 |
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| author | Ines Moreno-Gonzalez George A. Edwards Omar Hasan Nazaret Gamez Jonathan E. Schulz Juan Jose Fernandez-Valenzuela Antonia Gutierrez Claudio Soto Paul E. Schulz |
| author_facet | Ines Moreno-Gonzalez George A. Edwards Omar Hasan Nazaret Gamez Jonathan E. Schulz Juan Jose Fernandez-Valenzuela Antonia Gutierrez Claudio Soto Paul E. Schulz |
| author_sort | Ines Moreno-Gonzalez |
| collection | DOAJ |
| description | 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. <sup>18</sup>F-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 <sup>18</sup>F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo <sup>18</sup>F-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 <sup>18</sup>F-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. |
| first_indexed | 2024-03-10T06:37:47Z |
| format | Article |
| id | doaj.art-a40c51f851824a429b8fbc0b76530b08 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T06:37:47Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-a40c51f851824a429b8fbc0b76530b082023-11-22T17:58:06ZengMDPI AGDiagnostics2075-44182021-10-011110187410.3390/diagnostics11101874Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral StudyInes Moreno-Gonzalez0George A. Edwards1Omar Hasan2Nazaret Gamez3Jonathan E. Schulz4Juan Jose Fernandez-Valenzuela5Antonia Gutierrez6Claudio Soto7Paul E. Schulz8Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Cell Biology, Instituto de Investigacion Biomedica de Malaga-IBIMA, Faculty of Sicences, University of Malaga, 29010 Malaga, SpainDepartment of Cell Biology, Instituto de Investigacion Biomedica de Malaga-IBIMA, Faculty of Sicences, University of Malaga, 29010 Malaga, SpainDepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Neurology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USASeveral 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. <sup>18</sup>F-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 <sup>18</sup>F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo <sup>18</sup>F-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 <sup>18</sup>F-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.https://www.mdpi.com/2075-4418/11/10/1874PET imagingTauTHK5351tracerbiomarkerhistological assessment |
| spellingShingle | Ines Moreno-Gonzalez George A. Edwards Omar Hasan Nazaret Gamez Jonathan E. Schulz Juan Jose Fernandez-Valenzuela Antonia Gutierrez Claudio Soto Paul E. Schulz Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study Diagnostics PET imaging Tau THK5351 tracer biomarker histological assessment |
| title | Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study |
| title_full | Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study |
| title_fullStr | Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study |
| title_full_unstemmed | Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study |
| title_short | Longitudinal Assessment of Tau-Associated Pathology by <sup>18</sup>F-THK5351 PET Imaging: A Histological, Biochemical, and Behavioral Study |
| title_sort | longitudinal assessment of tau associated pathology by sup 18 sup f thk5351 pet imaging a histological biochemical and behavioral study |
| topic | PET imaging Tau THK5351 tracer biomarker histological assessment |
| url | https://www.mdpi.com/2075-4418/11/10/1874 |
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