Associations between inflammation and striatal dopamine D2-receptor availability in aging
Abstract Background Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is asso...
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03355-0 |
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| author | Vanessa Crine Goran Papenberg Jarkko Johansson Carl-Johan Boraxbekk Anders Wåhlin Ulman Lindenberger Martin Lövdén Katrine Riklund Lars Bäckman Lars Nyberg Nina Karalija |
| author_facet | Vanessa Crine Goran Papenberg Jarkko Johansson Carl-Johan Boraxbekk Anders Wåhlin Ulman Lindenberger Martin Lövdén Katrine Riklund Lars Bäckman Lars Nyberg Nina Karalija |
| author_sort | Vanessa Crine |
| collection | DOAJ |
| description | Abstract Background Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability. Methods Analyses were performed in a sample of healthy adults > 60 years assessed at two measurement occasions separated by 5 years. At both occasions, DRD2 availability was estimated by 11C-raclopride PET, and white-matter lesions by MRI. Inflammation was assessed by two C-reactive protein-associated DNA methylation scores at study baseline. Results Individuals with higher DNA methylation scores at baseline showed reduced striatal DRD2 availability. An interaction was found between DNA methylation scores and sex in relation to striatal DRD2 availability, such that associations were found in men but not in women. DNA methylation scores at study entrance were not significantly associated with 5-year striatal DRD2 decline rates. No significant association was found between DNA methylation scores and white-matter lesions, but higher scores as well as higher lesion burden were independently associated with reduced striatal DRD2 availability in men. Conclusions These findings suggest negative associations between one proxy of inflammation and DRD2 availability in older adults, selectively for men who had higher DNA methylation scores. Future studies should investigate other inflammatory markers in relation to dopamine integrity. |
| format | Article |
| id | doaj-art-6cef485fb47d4c85946a50a3fe42b683 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-6cef485fb47d4c85946a50a3fe42b6832025-02-02T12:34:57ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111210.1186/s12974-025-03355-0Associations between inflammation and striatal dopamine D2-receptor availability in agingVanessa Crine0Goran Papenberg1Jarkko Johansson2Carl-Johan Boraxbekk3Anders Wåhlin4Ulman Lindenberger5Martin Lövdén6Katrine Riklund7Lars Bäckman8Lars Nyberg9Nina Karalija10Department of Medical and Translational Biology, Umeå universityAging Research Center, Karolinska Institute and Stockholm UniversityUmeå Center for Functional Brain Imaging (UFBI), Umeå UniversityUmeå Center for Functional Brain Imaging (UFBI), Umeå UniversityUmeå Center for Functional Brain Imaging (UFBI), Umeå UniversityCenter for Lifeorgdivision Psychology, Max Planck Institute for Human DevelopmentDepartment of Psychology, University of GothenburgUmeå Center for Functional Brain Imaging (UFBI), Umeå UniversityAging Research Center, Karolinska Institute and Stockholm UniversityDepartment of Medical and Translational Biology, Umeå universityDepartment of Medical and Translational Biology, Umeå universityAbstract Background Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability. Methods Analyses were performed in a sample of healthy adults > 60 years assessed at two measurement occasions separated by 5 years. At both occasions, DRD2 availability was estimated by 11C-raclopride PET, and white-matter lesions by MRI. Inflammation was assessed by two C-reactive protein-associated DNA methylation scores at study baseline. Results Individuals with higher DNA methylation scores at baseline showed reduced striatal DRD2 availability. An interaction was found between DNA methylation scores and sex in relation to striatal DRD2 availability, such that associations were found in men but not in women. DNA methylation scores at study entrance were not significantly associated with 5-year striatal DRD2 decline rates. No significant association was found between DNA methylation scores and white-matter lesions, but higher scores as well as higher lesion burden were independently associated with reduced striatal DRD2 availability in men. Conclusions These findings suggest negative associations between one proxy of inflammation and DRD2 availability in older adults, selectively for men who had higher DNA methylation scores. Future studies should investigate other inflammatory markers in relation to dopamine integrity.https://doi.org/10.1186/s12974-025-03355-0InflammationDopamine D2-receptor availabilityPositron emission tomographyWhite-matter lesionsAging |
| spellingShingle | Vanessa Crine Goran Papenberg Jarkko Johansson Carl-Johan Boraxbekk Anders Wåhlin Ulman Lindenberger Martin Lövdén Katrine Riklund Lars Bäckman Lars Nyberg Nina Karalija Associations between inflammation and striatal dopamine D2-receptor availability in aging Journal of Neuroinflammation Inflammation Dopamine D2-receptor availability Positron emission tomography White-matter lesions Aging |
| title | Associations between inflammation and striatal dopamine D2-receptor availability in aging |
| title_full | Associations between inflammation and striatal dopamine D2-receptor availability in aging |
| title_fullStr | Associations between inflammation and striatal dopamine D2-receptor availability in aging |
| title_full_unstemmed | Associations between inflammation and striatal dopamine D2-receptor availability in aging |
| title_short | Associations between inflammation and striatal dopamine D2-receptor availability in aging |
| title_sort | associations between inflammation and striatal dopamine d2 receptor availability in aging |
| topic | Inflammation Dopamine D2-receptor availability Positron emission tomography White-matter lesions Aging |
| url | https://doi.org/10.1186/s12974-025-03355-0 |
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