Cerebrospinal fluid and positron-emission tomography biomarkers for noradrenergic dysfunction in neurodegenerative diseases: a systematic review and meta-analysis

Elisa Lancini; Lena Haag; Franziska Bartl; Maren Rühling; Nicholas J Ashton; Henrik Zetterberg; Emrah Düzel; Dorothea Hämmerer; Matthew J Betts

doi:10.1093/braincomms/fcad085

Cerebrospinal fluid and positron-emission tomography biomarkers for noradrenergic dysfunction in neurodegenerative diseases: a systematic review and meta-analysis

Brain Commun. 2023 Mar 29;5(3):fcad085. doi: 10.1093/braincomms/fcad085. eCollection 2023.

Authors

Elisa Lancini^{1

2}, Lena Haag^{1

2}, Franziska Bartl², Maren Rühling², Nicholas J Ashton^{3

4

5

6}, Henrik Zetterberg^{7

8

9

10

11}, Emrah Düzel^{1

2

12

13}, Dorothea Hämmerer^{1

2

12

13

14}, Matthew J Betts^{1

2

13}

Affiliations

¹ German Center for Neurodegenerative Diseases (DZNE), Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
² Faculty of Medicine, Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
³ Institute of Psychiatry, Department of Old Age Psychiatry, King's College London, London, UK.
⁴ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁷ Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁰ UK Dementia Research Institute at UCL, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹² Institute of Cognitive Neuroscience, University College London, London, UK.
¹³ Center for Behavioral Brain Sciences, University of Magdeburg, Magdeburg, Germany.
¹⁴ Department of Psychology, University of Innsbruck, Innsbruck, Austria.

Abstract

The noradrenergic system shows pathological modifications in aging and neurodegenerative diseases and undergoes substantial neuronal loss in Alzheimer's disease and Parkinson's disease. While a coherent picture of structural decline in post-mortem and in vivo MRI measures seems to emerge, whether this translates into a consistent decline in available noradrenaline levels is unclear. We conducted a meta-analysis of noradrenergic differences in Alzheimer's disease dementia and Parkinson's disease using CSF and PET biomarkers. CSF noradrenaline and 3-methoxy-4-hydroxyphenylglycol levels as well as noradrenaline transporters availability, measured with PET, were summarized from 26 articles using a random-effects model meta-analysis. Compared to controls, individuals with Parkinson's disease showed significantly decreased levels of CSF noradrenaline and 3-methoxy-4-hydroxyphenylglycol, as well as noradrenaline transporters availability in the hypothalamus. In Alzheimer's disease dementia, 3-methoxy-4-hydroxyphenylglycol but not noradrenaline levels were increased compared to controls. Both CSF and PET biomarkers of noradrenergic dysfunction reveal significant alterations in Parkinson's disease and Alzheimer's disease dementia. However, further studies are required to understand how these biomarkers are associated to the clinical symptoms and pathology.

Keywords: Alzheimer’s disease; Parkinson’s disease; locus coeruleus; noradrenaline; norepinephrine.

Publication types

Review

Abstract

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