Cerebrospinal fluid
Seeding aggregation assays, such as protein-misfolding cyclic
amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC),
detect misfolded proteins prone to aggregation by exploiting their
prion-like behavior [16]. In PD, the total concentration of a-syn in
the CSF seems to be lower, whereas the CSF levels of a-syn oligomers and
phosphorylated a-syn are elevated as compared with healthy controls
[9, 17]. These measures can serve as useful biomarkers for the early
detection of Lewy body disorders and distinguishing PD from Alzheimer’s
disease [18].
The activity of various lysosomal enzymes is changed in the CSF of PD
patients as compared to healthy controls [9]. Mutations inGBA1 gene cause changes in beta-glucocerebrosidase activity and
levels of glycosphingolipids in various body fluids which underlines
development of GBA-associated PD and can be measured to diagnose this
subtype of the disease [19]. The diagnostic accuracy can be improved
when combining several lysosomal enzyme activity measurements, and
further increased when Aβ, tau and a-syn pathology markers are added to
the model [20, 21]. Defining the subtype of prodromal PD may guide
future neurorestorative therapies [22].
Reduced levels of circulating cell-free mitochondrial DNA measured from
the CSF of PD patients have also been proposed as a potential biomarker
for the disease onset and progression, but several factors such as
concomitant treatments and comorbidities are likely to confound the
reliability of the readout [23, 24].