Fluid and Biopsy Based Biomarkers in Parkinson's Disease

Several advances in fluid and tissue-based biomarkers for use in Parkinson's disease (PD) and other synucleinopathies have been made in the last several years. While work continues on species of alpha-synuclein (aSyn) and other proteins which can be measured from spinal fluid and plasma samples, immunohistochemistry and immunofluorescence from peripheral tissue biopsies and alpha-synuclein seeding amplification assays (aSyn-SAA: including real-time quaking induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA)) now offer a crucial advancement in their ability to identify aSyn species in PD patients in a categorical fashion (i.e., of aSyn + vs aSyn -); to augment clinical diagnosis however, aSyn-specific assays that have quantitative relevance to pathological burden remain an unmet need. Alzheimer's disease (AD) co-pathology is commonly found postmortem in PD, especially in those who develop dementia, and dementia with Lewy bodies (DLB). Biofluid biomarkers for tau and amyloid beta species can detect AD co-pathology in PD and DLB, which does have relevance for prognosis, but further work is needed to understand the interplay of aSyn tau, amyloid beta, and other pathological changes to generate comprehensive biomarker profiles for patients in a manner translatable to clinical trial design and individualized therapies.