Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

Abstract

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD.

Lysosomal Dysfunction and α‐Synuclein Aggregation in Parkinson's Disease: Diagnostic Links

“…As CSF proteins may mirror the pathological processes in the PD brain, proteins involved in oxidative stress, inflammation, and protein aggregation—including α‐synuclein, amyloid‐beta, and (phospho)tau—as well as neurotransmitters in the CSF have been proposed as diagnostic biomarkers for PD . Several research groups have investigated the potential of lysosomal hydrolases as diagnostic biomarkers for AD and PD.…”

Vascular retinal biomarkers improves the detection of the likely cerebral amyloid status from hyperspectral retinal images

“…Spectral domain optical coherence tomography is currently being applied to various CNS neurodegenerative diseases [10] by measuring retinal nerve fibre layer loss and has been demonstrated to show nerve fiber anomalies in AD [11–14]. However, the method may lack specificity, as nerve fiber alterations are also observed in glaucoma, MCI [13], and Parkinson's disease [15,16].…”

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.…”

“…71,128,129 In a secondary analysis of the DATATOP study, lower baseline CSF α-syn levels predicted a better preservation of cognitive functions in early PD patients after 8-year-follow-up. 72 Another analysis of the DATATOP study found an association between higher phosphorylated-tau protein and greater decline in cognitive functions but slower motor progression. 130,131 Thus, it is clear that the role of tau protein is largely unknown, and, so far there are only association studies, not providing possible explanations on the importance of tau species in PD pathogenesis.…”