Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease
Abstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Translational Neurodegeneration |
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| Online Access: | https://doi.org/10.1186/s40035-024-00400-5 |
| _version_ | 1797273490352504832 |
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| author | Chen-Pei Lin Irene Frigerio John G. J. M. Bol Maud M. A. Bouwman Alex J. Wesseling Martin J. Dahl Annemieke J. M. Rozemuller Ysbrand D. van der Werf Petra J. W. Pouwels Wilma D. J. van de Berg Laura E. Jonkman |
| author_facet | Chen-Pei Lin Irene Frigerio John G. J. M. Bol Maud M. A. Bouwman Alex J. Wesseling Martin J. Dahl Annemieke J. M. Rozemuller Ysbrand D. van der Werf Petra J. W. Pouwels Wilma D. J. van de Berg Laura E. Jonkman |
| author_sort | Chen-Pei Lin |
| collection | DOAJ |
| description | Abstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD. Methods Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD, 14 PD, and 8 control brain donors. Fractional anisotropy (FA) and mean diffusivity were derived from the LC, and from tracts between the LC and the anterior cingulate cortex, the dorsolateral prefrontal cortex (DLPFC), the primary motor cortex (M1) or the hippocampus. Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase (DBH) to quantify noradrenergic cell density and fiber load. Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations. Results The AD and PD cases showed loss of LC noradrenergic cells and fibers. In the cortex, the AD cases showed increased DBH + immunoreactivity in the DLPFC compared to PD cases and controls, while PD cases showed reduced DBH + immunoreactivity in the M1 compared to controls. Higher FA within the LC was found for AD, which was correlated with loss of noradrenergic cells and fibers in the LC. Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group, whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group. The tract alterations were not correlated with cortical DBH + immunoreactivity. Conclusions In AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex. |
| first_indexed | 2024-03-07T14:45:07Z |
| format | Article |
| id | doaj.art-d072a13e824f4775bc8fbafeb9002b95 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-03-07T14:45:07Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-d072a13e824f4775bc8fbafeb9002b952024-03-05T20:05:22ZengBMCTranslational Neurodegeneration2047-91582024-02-0113111710.1186/s40035-024-00400-5Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s diseaseChen-Pei Lin0Irene Frigerio1John G. J. M. Bol2Maud M. A. Bouwman3Alex J. Wesseling4Martin J. Dahl5Annemieke J. M. Rozemuller6Ysbrand D. van der Werf7Petra J. W. Pouwels8Wilma D. J. van de Berg9Laura E. Jonkman10Amsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamCenter for Lifespan Psychology, Max Planck Institute for Human DevelopmentAmsterdam UMC, Department of Pathology, Location Vrije Universiteit AmsterdamAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAmsterdam Neuroscience, Brain imagingAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAmsterdam UMC, Department of Anatomy and Neurosciences, Location Vrije Universiteit AmsterdamAbstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD. Methods Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD, 14 PD, and 8 control brain donors. Fractional anisotropy (FA) and mean diffusivity were derived from the LC, and from tracts between the LC and the anterior cingulate cortex, the dorsolateral prefrontal cortex (DLPFC), the primary motor cortex (M1) or the hippocampus. Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase (DBH) to quantify noradrenergic cell density and fiber load. Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations. Results The AD and PD cases showed loss of LC noradrenergic cells and fibers. In the cortex, the AD cases showed increased DBH + immunoreactivity in the DLPFC compared to PD cases and controls, while PD cases showed reduced DBH + immunoreactivity in the M1 compared to controls. Higher FA within the LC was found for AD, which was correlated with loss of noradrenergic cells and fibers in the LC. Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group, whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group. The tract alterations were not correlated with cortical DBH + immunoreactivity. Conclusions In AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex.https://doi.org/10.1186/s40035-024-00400-5Locus coeruleusNoradrenergic degenerationAlzheimer’s diseaseParkinson’s diseaseDiffusion MRIPost-mortem |
| spellingShingle | Chen-Pei Lin Irene Frigerio John G. J. M. Bol Maud M. A. Bouwman Alex J. Wesseling Martin J. Dahl Annemieke J. M. Rozemuller Ysbrand D. van der Werf Petra J. W. Pouwels Wilma D. J. van de Berg Laura E. Jonkman Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease Translational Neurodegeneration Locus coeruleus Noradrenergic degeneration Alzheimer’s disease Parkinson’s disease Diffusion MRI Post-mortem |
| title | Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease |
| title_full | Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease |
| title_fullStr | Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease |
| title_full_unstemmed | Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease |
| title_short | Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease |
| title_sort | microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in alzheimer s disease and parkinson s disease |
| topic | Locus coeruleus Noradrenergic degeneration Alzheimer’s disease Parkinson’s disease Diffusion MRI Post-mortem |
| url | https://doi.org/10.1186/s40035-024-00400-5 |
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