Diagnostic cerebrospinal fluid biomarkers for Parkinson's disease: A pathogenetically based approach

Abstract

The inaccuracy of the early diagnosis of Parkinson's disease (PD) has been a major incentive for studies aimed at the identification of biomarkers. Brain-derived cerebrospinal fluid (CSF) proteins are potential biomarkers considering the major role that proteins play in PD pathogenesis. In this review, we discuss the current hypotheses about the pathogenesis of PD and identify the most promising candidate biomarkers among the CSF proteins studied so far. The list of potential markers includes proteins involved in various pathogenetic processes, such as oxidative stress and protein aggregation. This list will undoubtedly grow in the near future by application of CSF proteomics and subsequent validation of identified proteins. Probably a single biomarker will not suffice to reach high sensitivity and specificity, because PD is pathogenetically heterogeneous and shares etiological factors with other neurodegenerative diseases. Furthermore, identified candidate biomarkers will have to be thoroughly validated before they can be implemented as diagnostic aids.

Biomarkers of Parkinson's disease: recent insights, current challenges, and future prospects

“…70 Regarding α-syn, the majority of recent studies have shown decreased CSF levels in PD patients, as compared to controls, although this marker apparently cannot distinguish among different synucleopathies. [71][72][73] In addition, levels of CSF tau protein were higher in PD patients, in particular in the early phases, as compared to controls. 74 Among other CSF biomarkers, DJ-1 levels were found to increase in early PD patients compared to controls.…”

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

“…Today, the strongest evidence for the causation of PD suggests a multifactorial intervention of genetic and environmental factors, with possible mechanisms ranging from mitochondrial dysfunction, oxidative stress, protein aggregation, impaired protein degradation, dysregulated autophagy, and inflammation [5]. Given the diversity of possible disease mechanisms, biomarkers related to pathogenesis offer the most promising approaches for early diagnosis of PD (Table 1).…”

“…Evidence suggests that defects of the respiratory chain (complex I), increased accumulation of mitochondrial DNA mutations, abnormal mitochondrial calcium homoeostasis, defective autophagic removal of mitochondria (mitophagy), and increased oxidative stress are all involved in the pathogenesis of PD [5].…”

“…Increased levels of proinflammatory cytokines and alterations in growth factor levels in CSF or plasma of PD patients are molecular indicators of inflammation. This is evidenced by increased CSF levels of several interleukins (ILs), including IL-1-β, IL-6 and IL-8, and decreased levels of the components of the complement system in PD patients [5]. Furthermore, it was found that high-sensitivity C-reactive protein (hs-CRP) levels in the early PD group were higher than those in healthy controls [32].…”

CFS Biomarkers in Parkinson’s Disease

“…The evidences for the implication of mitochondrial dysfunction and increased oxidative stress in the pathogenesis of PD are several (Schapira, 2008;Van Dijk et al, 2010): (i) mitochondrial complex I activity is reduced in the substantia nigra (Schapira et al, 1989); (ii) MPTP and rotenone toxicity is mediated via mitochondrial complex I inhibition (Tipton & Singer, 1993;Betarbet et al, 2003); (iii) mitochondrial-related proteins, such as prohibitin, ATP synthase and superoxide dismutase (SOD2), are altered in the nigra and frontal cortex of PD patients (Ferrer et al, 2007); and (iv) some monogenic forms of PD are caused by mutations of DJ-1 (Bonifati et al, 2003), PINK-1 (Valente et al, 2004), LRRK2 (Paisán-Ruíz et al, 2004Zimprich et al, 2004), all implicated in the mitochondrial function and oxidative stress (Lin & Beal, 2006). Thus, attention has been focused on markers linked to the mitochondrial dysfunction and oxidative stress.…”