Recent advances in fluid and tissue-based biomarkers for use in Parkinson’s disease

Parkinson's disease (PD) is a common neurodegenerative disease leading to motor and non-motor disabilities. Broadly accessible fluid- or tissue-based biomarkers will complement neuroimaging and may allow earlier identification and more precise tracking. The authors have reviewed the recent advances from original full-text English-language articles that were indexed in the PubMed database between June 2023 and June 2024. Articles were identified using the PubMed MESH terms 'Parkinson's Disease' AND 'biomarkers' that focused on using a fluid or tissue-based biomarker to distinguish participants with PD from healthy controls or other conditions. The most promising new biomarkers are those measuring α-synuclein from cerebrospinal fluid or skin biopsy. A significant limitation of these studies is their reliance on a clinical diagnosis of PD, mostly without neuropathological confirmation. Mounting evidence supports the validity of CSF and skin biopsy-based detection of α-synuclein for the distinction of PD from healthy controls, although not yet from the spectrum of α-synucleinopathies nor from non-α-synuclein forms of parkinsonism. Nonetheless, the potential to detect individuals who will develop PD may revolutionize our ability to test potential preventive interventions before motor symptoms develop. Machine-learning approaches offer promising strategies for efficient identification and validation of novel biomarkers.