Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease

Abstract

ObjectiveThe purpose of this study was to investigate whether cerebrospinal fluid (CSF) levels of tau, phosphorylated tau, β‐amyloid42, α‐synuclein, neurofilament light, and YKL‐40 change over time and if changes correlate with motor progression and/or cognitive decline in patients with PD and controls.MethodsWe included 63 patients with PD (nondemented) and 21 neurologically healthy controls from the prospective and longitudinal Swedish BioFINDER study, all of whom had clinical assessments and lumbar punctures at baseline and after 2 years.ResultsCSF tau levels correlated strongly with α‐synuclein. The levels of CSF α‐synuclein, tau, phosphorylated tau, neurofilament light, and YKL‐40, but not β‐amyloid42, increased in CSF over 2 years in PD. No changes were seen in the control group. Studying patients with a short disease duration ( ≤ 5 years) and patients with a long disease duration ( > 5 years) separately, α‐synuclein and tau only increased in the PD group with long disease duration. In the PD group, an increase in phosphorylated tau over 2 years correlated with faster motor progression and faster cognitive decline. An increase in YKL‐40 over 2 years correlated with faster cognitive decline.ConclusionCSF biomarkers reflecting Lewy body pathology and neurodegeneration (α‐synuclein), neuronal degeneration (tau, phosphorylated tau, and neurofilament light), and inflammation (YKL‐40) increase significantly over 2 years in PD. CSF levels of α‐synuclein and tau correlate and remain stable in the early symptomatic phase of PD but increase in the later phase. We hypothesize that CSF α‐synuclein levels might increase as a result of more intense neurodegeneration in PD with long disease duration. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Serum soluble lymphocyte activation gene‐3 as a diagnostic biomarker in Parkinson's disease: A pilot multicenter study

“…Moreover, immune response and inflammatory factors have an impact on NMS diversity in PD as well . Increased inflammatory factors were associated with cognitive decline, rapid eye movement sleep behavior disorder, fatigue, and depression in a previous study . Because sLAG‐3 is an indicator of cellular immunity related to cytokine secretion, it could reflect the degree of inflammatory response in patients with PD.…”

“…Increasing numbers of studies have focused on fluid biomarkers for Parkinson's disease (PD) using easily accessible sample sources such as serum and include α‐synuclein (α‐syn), DJ‐1, dopamine metabolites, factors related to oxidative stress, and inflammatory cytokines . However, the results of these studies were inconsistent with previous studies .…”

Cognitive decline in Parkinson disease

“…In one study of CSF biomarker change with time, Hall et al . 102 found that levels of t-tau, p-tau, total α-synuclein, neurofilament and YKL-40 (a marker of inflammation), but not Aβ 42 , increased over a 2-year period and were associated with worsening cognition, and the increase was particularly marked in patients with longer disease duration. These findings are consistent with reports that α-synuclein levels increase with more severe neurodegeneration.…”

Longitudinal analyses of cerebrospinal fluid α‐Synuclein in prodromal and early Parkinson's disease

“…We recently reported that CSF α‐syn levels in de novo PD showed minimal change over 12 months . Longitudinal changes in CSF α‐syn and other biomarkers have been examined in other PD cohorts for up to 2 years with discrepant findings . Subject selection, preanalytical factors, and different assays may have contributed to discrepancies (see Discussion).…”