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].