Differences in Blood and Cerebrospinal Fluid Between Parkinson's Disease and Related Diseases

It is difficult to distinguish Parkinson's disease (PD) in the early stage from those of various disorders including atypical Parkinson's syndrome (APS), vascular parkinsonism (VP), and even essential tremor (ET), because of the overlap of symptoms. Other, more challenging problems will arise when Parkinson's disease develops into Parkinson's disease dementia (PDD) in the middle and late stages. At this time, the differential diagnosis of PDD and DLB becomes thorny. These complicate the diagnostic process for PD, which traditionally heavily relies on symptomatic assessment and treatment response. Recent advances have identified several biomarkers in the blood and cerebrospinal fluid (CSF), including α-synuclein, lysosomal enzymes, fatty acid-binding proteins, and neurofilament light chain, whose concentration differs in PD and the related diseases. However, not all these molecules can effectively discriminate PD from related disorders. This review advocates for a paradigm shift toward biomarker-based diagnosis to effectively distinguish between PD and similar conditions. These biomarkers may reflect the diversity that exist among different diseases and provide an effective way to accurately understand their mechanisms. This review focused on blood and CSF biomarkers of PD that may have differential diagnostic value and the related molecular measurement methods with high diagnostic performance due to emerging technologies.