Blood and cerebrospinal fluid differences between Parkinson's disease and related diseases

Accurately diagnosing Parkinson’s disease (PD) in its early stages is difficult due to its symptoms overlapping with those of various disorders, including atypical Parkinsonian syndromes, dementia with Lewy bodies (DLB), and even essential tremor. This complicates 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, that may potentially be used to diagnosed PD. However, not all can effectively distinguish PD from related disorders or identify its subtypes. This review advocates for a paradigm shift towards biomarker-based diagnosis to effectively distinguish between PD and similar conditions and to categorize PD into its subtypes. These biomarkers may reflect the differences 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.