CSF and PET biomarkers for noradrenergic dysfunction in neurodegenerative diseases: a systematic review and meta-analysis

The noradrenergic system shows pathological modifications in aging and neurodegenerative diseases and is thought to be affected in the early stages of both Alzheimer and Parkinson's diseases. We conducted a meta-analysis of noradrenergic differences in Alzheimer's disease type dementia (ADD) and Parkinson's disease (PD) using CSF and PET biomarkers. CSF noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) as well as NA transporter availability (PET MeNER) levels in controls, ADD and PD patients was summarized from 26 articles (1025 patients and 839 controls in total) using a random-effects model meta-analysis. Compared with controls, PD patients showed significant reductions in CSF NA and MHPG, and PET MeNER binding in the hypothalamus. In ADD, MHPG levels were increased compared with controls. Age correlated with CSF MHPG levels in ADD, but not in PD. Noradrenergic dysfunction in neurodegenerative diseases can be detected using CSF or PET measures and may be more pronounced in PD compared to ADD.