Brain-Biomarker Changes in Body Fluids of Patients with Parkinson's Disease

Abstract

Parkinson's disease (PD) is an incurable neurodegenerative disease that is rarely diagnosed at an early stage. Although the understanding of PD-related mechanisms has greatly improved over the last decade, the diagnosis of PD is still based on neurological examination through the identification of motor symptoms, including bradykinesia, rigidity, postural instability, and resting tremor. The early phase of PD is characterized by subtle symptoms with a misdiagnosis rate of approximately 16-20%. The difficulty in recognizing early PD has implications for the potential use of novel therapeutic approaches. For this reason, it is important to discover PD brain biomarkers that can indicate early dopaminergic dysfunction through their changes in body fluids, such as saliva, urine, blood, or cerebrospinal fluid (CSF). For the CFS-based test, the invasiveness of sampling is a major limitation, whereas the other body fluids are easier to obtain and could also allow population screening. Following the identification of the crucial role of alpha-synuclein (α-syn) in the pathology of PD, a very large number of studies have summarized its changes in body fluids. However, methodological problems have led to the poor diagnostic/prognostic value of this protein and alternative biomarkers are currently being investigated. The aim of this paper is therefore to summarize studies on protein biomarkers that are alternatives to α-syn, particularly those that change in nigrostriatal areas and in biofluids, with a focus on blood, and, eventually, saliva and urine.

Keywords: Parkinson’s disease; VGF; early diagnosis.

Figure 1

Brain-biomarker changes in bodily fluids of PD patients. Figure legend: The figure shows proteins that change in the brain (nigrostriatal areas) and bodily fluids (plasma, saliva, and urine) of PD patients. NF-L and ChA were found to be abnormally aggregated in the brain and increased in the blood. SP and P11 decreased in the brain (and SP also decreased in sputum), but increased in the blood, while GFAP and NT increased in both the brain and blood. In contrast, VGF decreased in the brain, but also in blood and urine. NF-L: neurofilament light protein; SP: substance P; P11: S100A10 (S100 calcium-binding protein A10); NT: neurotensin; ChA: Chromogranin A; VGF: no acronym; GFAP: glial fibrillary acidic protein. Upward arrow: increase; downward arrow: decrease.