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.

Transcriptomics effects of per- and polyfluorinated alkyl substances in differentiated neuronal cells

“…Recent studies demonstrated that changes in protein expression related to neurodegenerative diseases can be measured in peripheral body fluids such as blood and saliva. 54, 55 It has also been shown that damage to the BBB can lead to release of proteins from the brain to the blood 56 . Further, PFAS can disrupt the BBB through oxidative stress and may also lead to this leakage.…”

“…59 Recent studies have shown that changes in protein expression related to neurodegenerative diseases can be measured in peripheral body fluids such as blood and saliva. 60,61 It has also been shown that damage to the BBB in certain neurodegenerative diseases leads to the movement of biomarkers out of the brain into the blood 62 . As such, it is possible to capture disruptions in the nervous system via monitoring changes in other tissues, most practically in blood.…”

Early identification of Parkinson’s disease with anxiety based on combined clinical and MRI features

“…Electrophysiology, including electroencephalograms and electromyography, can also reflect motor symptom severity and pharmaceutical effects in PD patients ( Waninger et al, 2020 ; Betrouni et al, 2022 ). Previous studies have also shown that saliva, urine, blood, and cerebrospinal fluid (CSF) biomarkers can help identify patients with PD and aid in disease monitoring and subtype characterization ( Maass et al, 2019 ; Cocco et al, 2023 ; Xiang et al, 2024 ). However, whether these markers can be used to identify cases of co-morbid PD and anxiety needs further study.…”

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

“…Among the ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are potential biomarkers of PD ( Kuo et al, 2021 ). However, a single biomarker cannot fully elucidate the pathological mechanism of PD and fails to attain the high specificity and sensitivity required for accurate diagnosis ( Cocco et al, 2023 ). Numerous studies on PD have proposed integrated biomarkers based on the competing endogenous RNA (ceRNA) hypothesis, which explains the competition between coding RNAs (mRNAs) and ncRNAs for shared miRNAs ( Lin et al, 2021 ).…”