REM sleep behavior disorder and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau and phosphorylated tau in Parkinson’s disease: a cross-sectional and longitudinal study

• Published in: Journal of neurology Vol. 269; no. 9; pp. 4836 - 4845
• Main Authors: Nabizadeh, Fardin, Pirahesh, Kasra, Valizadeh, Parya
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2022; Springer Nature B.V
• Subjects: Behavior disorders; Biomarkers; Cerebrospinal fluid; Cognitive ability; Dementia disorders; Longitudinal studies; Medicine; Medicine & Public Health; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Original Communication; Parkinson's disease; Protein interaction; REM sleep; Sleep disorders; Synuclein; Tau protein; Tau; Cerebrospinal fluid (CSF); Parkinson’s disease; Alpha-synuclein; Beta-amyloid
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-022-11120-z

Background
Proteinopathies as a consequence of cellular pathological pathways associated with Parkinson's disease (PD), leading to alteration of protein aggregation in cerebrospinal fluid (CSF). Rapid eye movement (REM) sleep behavior disorder (RBD is generally accepted as a prognostic factor predicting neurodegeneration, worse cognitive impairment, and the development of dementia PD.
Aim
Here we aimed to investigate the difference and longitudinal alteration of the CSF level of α-synuclein (α-syn), amyloid βeta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with RBD and without RBD.
Methods
We entered 413 early stage PD patients and 187 healthy controls (HCs) from PPMI. We compared the level of CSF biomarkers at baseline, 6 months, 1 year, and 2 years visits. In addition, we used linear mixed models to assess longitudinal changes of CSF proteins over 6 months, 1 year, and 2 years within groups.
Results
The level of CSF α-syn, Aβ1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any timepoint. In addition, there was a significantly lower CSF Aβ1-42 in PD–RBD subjects at 2 years timepoint (
p
 = 0.020). There was no difference in CSF Aβ1-42 at other timepoints. Furthermore, comparisons between PD subjects with RBD and without RBD did not show any significant difference in CSF α-syn, t-tau, and p-tau at timepoints. The longitudinal analysis demonstrated that there was only a significant change in CSF level of Aβ1-42 after 1 year in PD patients with RBD (
p
 = 0.031).
Conclusions
In our study, baseline values and longitudinal changes in CSF α-syn, t-tau, and p-tau were not remarkable enough to distinguish PD patients with and without RBD. Both of these groups demonstrated a stable trend in the longitudinal changes of these biomarkers. However, CSF Aβ1-42 seems to decrease in short follow-up and represents a significant difference after a while in PD patients with and without RBD. These findings suggested that CSF Aβ1-42 could be a more sensitive biomarker for early neurodegeneration and cognitive impairment in PD patients. The stable trend in other CSF biomarkers such as α-syn, t-tau, and p-tau can be justified by the fact that severe neurodegeneration may not be predictable in the early stages of PD patients.