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The clinical diagnosis of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) is challenging due to highly variable clinical presentation and clinical and pathological overlap with other neurodegenerative diseases. Since cerebrospinal fluid (CSF) mirrors the pathological changes taking place in the brain, it represents a promising source of biomarkers. With respect to classical AD biomarkers, low CSF Aβ 42 levels have shown a robust prognostic value in terms of development of cognitive impairment in PD and DLB. In the differential diagnosis between AD and DLB, a potential role of t-tau, p-tau and Aβ 42 /Aβ 38 ratio has been demonstrated. Regarding CSF α-synuclein (α-syn) species, lower levels of total α-synuclein (t-α-syn) and higher concentration of oligomeric-α-synuclein (o-α-syn) and phosphorylated α-synuclein (p-α-syn) have been observed in PD. Furthermore, the detection of "pro-aggregating" α-synuclein has enabled the discrimination of patients affected by synucleinopathies with high sensitivity and specificity. New promising biomarkers are emerging: GCase activity (reduced in PD and DLB patients vs. controls), CSF/serum albumin ratio (increased in PD and DLB), fatty-acid-binding protein (increased in AD and DLB vs. PD), visinin-like protein-1 (increased in AD vs. DLB) and monoamines (useful in differential diagnosis among PD and DLB). These encouraging results need to be confirmed by future studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the management of Parkinson's disease, reliable diagnostic and prognostic biomarkers are urgently needed. The diagnosis of Parkinson's disease mostly relies on clinical symptoms, which hampers the detection of the earliest phases of the disease-the time at which treatment with forthcoming disease-modifying drugs could have the greatest therapeutic effect. Reliable prognostic markers could help in predicting the response to treatments. Evidence suggests potential diagnostic and prognostic value of CSF and blood biomarkers closely reflecting the pathophysiology of Parkinson's disease, such as α-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain. A combination of multiple CSF biomarkers has emerged as an accurate diagnostic and prognostic model. With respect to early diagnosis, the measurement of CSF α-synuclein aggregates is providing encouraging preliminary results. Blood α-synuclein species and neurofilament light chain are also under investigation because they would provide a non-invasive tool, both for early and differential diagnosis of Parkinson's disease versus atypical parkinsonian disorders, and for disease monitoring. In view of adopting CSF and blood biomarkers for improving Parkinson's disease diagnostic and prognostic accuracy, further validation in large independent cohorts is needed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lysosomal impairment is increasingly recognized as a central event in the pathophysiology of PD. Genetic associations between lysosomal storage disorders, including Gaucher disease and PD, highlight common risk factors and pathological mechanisms. Because the autophagy-lysosomal system is involved in the intralysosomal hydrolysis of dysfunctional proteins, lysosomal impairment may contribute to α-synuclein aggregation in PD. The degradation of α-synuclein is a complex process involving different proteolytic mechanisms depending on protein burden, folding, posttranslational modifications, and yet unknown factors. In this review, evidence for lysosomal dysfunction in PD and its intimate relationship with α-synuclein aggregation are discussed, after which the question of whether lysosomal proteins may serve as diagnostic biomarkers for PD is addressed. Changes in lysosomal enzymes, such as reduced glucocerebrosidase and cathepsin levels, have been observed in affected brain regions in PD patients. The detection of lysosomal proteins in CSF may provide a read-out of lysosomal dysfunction in PD and holds promise for the development of diagnostic PD biomarkers. Initial PD biomarker studies demonstrated altered lysosomal enzyme activities in CSF of PD patients when compared with controls. However, CSF lysosomal enzyme activities alone could not discriminate between PD patients and controls. The combination of CSF lysosomal markers with α-synuclein species and indicators of mitochondrial dysfunction, inflammation, and other pathological proteins in PD may be able to facilitate a more accurate diagnosis of PD. Further CSF biomarker studies are needed to investigate the utility of CSF lysosomal proteins as measures of disease state and disease progression in PD. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.)