Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease
Abstract Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer’s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. T...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01901-5 |
| _version_ | 1811291034003439616 |
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| author | Kristi Henjum Leiv Otto Watne Kristin Godang Nathalie Bodd Halaas Rannveig Saksholm Eldholm Kaj Blennow Henrik Zetterberg Ingvild Saltvedt Jens Bollerslev Anne Brita Knapskog |
| author_facet | Kristi Henjum Leiv Otto Watne Kristin Godang Nathalie Bodd Halaas Rannveig Saksholm Eldholm Kaj Blennow Henrik Zetterberg Ingvild Saltvedt Jens Bollerslev Anne Brita Knapskog |
| author_sort | Kristi Henjum |
| collection | DOAJ |
| description | Abstract Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer’s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOEε4 status verified the findings. In restricted analyses comparing A+T+ patients to A−T− cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A−T− cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin. |
| first_indexed | 2024-04-13T04:23:18Z |
| format | Article |
| id | doaj.art-abd9eef7cff74cff81f994fdf7c88c82 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-13T04:23:18Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-abd9eef7cff74cff81f994fdf7c88c822022-12-22T03:02:39ZengNature Publishing GroupTranslational Psychiatry2158-31882022-04-011211910.1038/s41398-022-01901-5Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological diseaseKristi Henjum0Leiv Otto Watne1Kristin Godang2Nathalie Bodd Halaas3Rannveig Saksholm Eldholm4Kaj Blennow5Henrik Zetterberg6Ingvild Saltvedt7Jens Bollerslev8Anne Brita Knapskog9Department of Geriatric Medicine, Institute of Clinical Medicine, Oslo University Hospital, Ullevaal, University of OsloDepartment of Geriatric Medicine, Oslo University Hospital, Ullevaal, OsloSection of Specialized Endocrinology, Department of Endocrinology, Oslo University HospitalDepartment of Geriatric Medicine, Institute of Clinical Medicine, Oslo University Hospital, Ullevaal, University of OsloDepartment of Neuromedicine and Movement Science, Norwegian University of Science and TechnologyDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Neuromedicine and Movement Science, Norwegian University of Science and TechnologySection of Specialized Endocrinology, Department of Endocrinology, Oslo University HospitalDepartment of Geriatric Medicine, Oslo University Hospital, Ullevaal, OsloAbstract Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer’s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOEε4 status verified the findings. In restricted analyses comparing A+T+ patients to A−T− cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A−T− cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.https://doi.org/10.1038/s41398-022-01901-5 |
| spellingShingle | Kristi Henjum Leiv Otto Watne Kristin Godang Nathalie Bodd Halaas Rannveig Saksholm Eldholm Kaj Blennow Henrik Zetterberg Ingvild Saltvedt Jens Bollerslev Anne Brita Knapskog Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease Translational Psychiatry |
| title | Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease |
| title_full | Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease |
| title_fullStr | Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease |
| title_full_unstemmed | Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease |
| title_short | Cerebrospinal fluid catecholamines in Alzheimer’s disease patients with and without biological disease |
| title_sort | cerebrospinal fluid catecholamines in alzheimer s disease patients with and without biological disease |
| url | https://doi.org/10.1038/s41398-022-01901-5 |
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