Exploring [11C]CPPC as a CSF1R-targeted PET Imaging Marker for Early Parkinson's Disease Severity.
| Title: | Exploring [11C]CPPC as a CSF1R-targeted PET Imaging Marker for Early Parkinson's Disease Severity. |
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| Authors: | Mills KA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Du Y; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Coughlin JM; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Foss CA; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Horti AG; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Jenkins K; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Skorobogatova Y; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Spiro E; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Motley CS; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Dannals RF; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Song JJ; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Choi YR; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Redding-Ochoa J; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Troncoso J; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Dawson VL; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Kam TI; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Pomper MG; Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology and Radiologic Science, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, US.; Department of Radiology, University of Texas Southwestern School of Medicine, Dallas, TX, USA (current).; Dawson TM; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, US. |
| Source: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 Feb 13. Date of Electronic Publication: 2024 Feb 13. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Neuroinflammation through enhanced innate immunity is thought play a role in the pathogenesis of Parkinson's disease (PD). Methods for monitoring neuroinflammation in living patients with PD are currently limited to positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. The colony stimulating factor 1 receptor (CSF1R) plays a crucial role in microglial function, an important cellular contributor to the nervous system's innate immune response. Using immunologic methods, we show that CSF1R in human brain is colocalized with the microglial marker, ionized calcium binding adaptor molecule 1 (Iba1). In PD, CSF1R immunoreactivity is significantly increased in PD across multiple brain regions, with the largest differences in the midbrain versus controls. Autoradiography revealed significantly increased [3H]JHU11761 binding in the inferior parietal cortex of PD patients. PET imaging demonstrated that higher [11C]CPPC binding in the striatum was associated with greater motor disability in PD. Furthermore, increased [11C]CPPC binding in various regions correlated with more severe motor disability and poorer verbal fluency. This study finds that CSF1R expression is elevated in PD and that [11C]CPPC-PET imaging of CSF1R is indicative of motor and cognitive impairments in the early stages of the disease. Moreover, the study underscores the significance of CSF1R as a promising biomarker for neuroinflammation in Parkinson's disease, suggesting its potential use for non-invasive assessment of disease progression and severity, leading to earlier diagnosis and targeted interventions. |
| Competing Interests: | Competing Interest Statement: Drs. Kelly Mills, Yong Du, and Robert Dannals as well as Katelyn Jenkins, Chelsie Motley, Ergi Sprio and Catherine Foss report no competing interest. Under a license agreement between D&D Pharmatech and the Johns Hopkins University, the University and Drs. Pomper, Coughlin and Horti are entitled to royalty distributions related to the technology described in the study discussed in this publication. Dr. Pomper has been and Dr. Horti hold equity in D&D Pharmatech. Dr. Pomper has been and Dr. Horti is a paid consultants to the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Dr. T. Dawson and V. Dawson hold shares of stock options as well as equity in D & D Pharmatech; These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. |
| Comments: | Update in: J Clin Invest. 2025 Apr 15;135(12):e186591. doi: 10.1172/JCI186591.. (PMID: 40232849) |
| Grant Information: | P30 AG066507 United States AG NIA NIH HHS; P41 EB024495 United States EB NIBIB NIH HHS; R01 AG066464 United States AG NIA NIH HHS; U19 AG033655 United States AG NIA NIH HHS |
| Contributed Indexing: | Keywords: Biological Sciences; Neuroscience; Parkinson’s disease; microglia; neuroinflammation |
| Entry Date(s): | Date Created: 20230703 Latest Revision: 20250616 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10312881 |
| DOI: | 10.1101/2023.05.28.23290647 |
| PMID: | 37398476 |
| Database: | MEDLINE |
Journal Article; Preprint