Peripheral body fluids
Plasma levels of a-syn species, neurofilaments, glial fibrillary acidic protein (GFAP), pTau181 and inflammatory cytokines have been studied as prospective biomarkers of PD [5]. Increased quantities of total a-syn, but no change in oligomeric and phosphorylated species of a-syn, have been measured in plasma from PD patients [25]. Extracellular vesicles isolated from blood and carrying a-syn oligomers and phosphorylated a-syn may bring new possibilities for the early diagnosis of PD [26]. Blood beta-synuclein may also have relevance since, unlike a-syn, it is not present in the blood of healthy individuals [27]. Additionally, the concentration of different a-syn species and DJ-1 in saliva have been proposed as potential easily accessible biomarkers [28]. However, the correlation between salivary a-syn and the presence or severity of PD have remained controversial.
Neurofilaments are abundant structural proteins exclusively expressed in nerve fibers. Upon axonal damage different subunits of neurofilaments are released to the interstitial space in the central nervous system (CNS) [29]. Neurofilament light chain (NfL) shows promise for the differential diagnosis of parkinsonian syndromes discriminating idiopathic PD from progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration [9, 29]. In a recent study, plasma levels of both NfL and GFAP correlated with motor symptoms of PD making them promising prognostic biomarker candidates [5]. Another PPMI study suggests serum uric acid as a potential prodromal marker of PD [30].
Neuroinflammation and increased endoplasmic reticulum (ER) stress are implicated in the pathogenesis of PD making serum immune and ER stress marker profiles potential tools for the follow-up of the disease state [31, 32]. However, their specificity to PD can be questioned as inflammatory cytokine levels and ER stress are elevated in a wide range of conditions [32]. Nevertheless, peripheral signs of inflammation should be considered for the biomarker battery of PD [31].
Reduced trophic factor support may underly early pathological steps in neurodegenerative diseases including PD. A meta-analysis by Rahmani et al. [33] suggested reduced serum levels of brain-derived neurotrophic factor (BDNF) in PD patients as compared to healthy controls and showed that BDNF downregulation is associated with progressive motor symptoms. Thus, we should not forget NTFs as potential diagnostic biomarkers of PD [32, 34].