Cerebrospinal fluid biomarkers in Parkinson’s disease with freezing of gait: an exploratory analysis

Abstract

We explore the association between three Alzheimer’s disease-related and ten inflammation-related CSF markers and freezing of gait (FOG) in patients with Parkinson’s disease (PD). The study population includes PD patients with FOG (PD-FOG, N = 12), without FOG (PD-NoFOG, N = 19), and healthy controls (HC, N = 12). Age and PD duration are not significantly different between groups. After adjusting for covariates and multiple comparisons, the anti-inflammatory marker, fractalkine, is significantly decreased in the PD groups compared to HC (P = 0.002), and further decreased in PD-FOG compared to PD-NoFOG (P = 0.007). The Alzheimer’s disease-related protein, Aβ42, is increased in PD-FOG compared to PD-NoFOG and HC (P = 0.001). Group differences obtained in individual biomarker analyses are confirmed with multivariate discriminant partial least squares regression (P < 0.001). High levels of Aβ42 in PD-FOG patients supports an increase over time from early to advanced state. Low levels of fractalkine might suggest anti-inflammatory effect. These findings warrant replication.

Reduced Norepinephrine Transporter Binding in Parkinson’s disease with dopa Responsive Freezing Gait

“…Similar results were obtained with additional linear mixed models performed post-hoc that: 53 as previously suggested by studies in non-human primates and several transgenic rodent models where the reduction of NE contributed to increased Aβ pathology [54][55][56] . Interestingly, the increased amyloid aggregation in these models was reversed by using droxidopa 57 .…”

“…The results also add to previous findings suggesting a connection between NA dysfunction and FOG. Further, this decreased NA innervation may relate to the recently reported increase in CSF Aβ42 amyloid in PD-FOG patients 53 as previously suggested by studies in non-human primates and several transgenic rodent models where the reduction of NE contributed to increased Aβ pathology 54-56 . Interestingly, the increased amyloid aggregation in these models was reversed by using droxidopa 57 .…”

Blood and Cerebrospinal Fluid Biomarkers of Inflammation in Parkinson’s Disease

“…One longitudinal study reports that higher CSF levels of MCP-1 and MMP-10 are associated with more severe motor impairment [88]. Contrary, lower levels of the anti-inflammatory marker fractalkine and IL-18 were associated with worse motor function [72,89].…”

Dementia with Lewy bodies: Impact of co‐pathologies and implications for clinical trial design

“…CSF assays and PET scans,[102][103][104] although, despite recent advances, there is still a lack of a sensitive and specific ligand for α-synuclein.Several studies show that PD individuals present lower CSF tau levels than controls [105][106][107]. It is unclear what the reason is for this phenomenon or whether this occurs in DLB.…”