Many biomarkers for PD fail to inform on progression

By Lucy Piper

Longitudinal monitoring of 30 tests for marker candidates in early Parkinson's disease (PD) has found that just 10 show significant changes commensurate with disease progression.

"The fact that we identified no more than 33% of the markers analyzed having significantly changed during our 24-month observational period highlights the mandate of finding reliable progression markers", say lead researcher Brit Mollenhauer (Paracelsus-Elena-Klinik, Kassel, Germany) and team in Neurology.

"These results have immediate consequences for clinical research in PD by restricting the potential usage of some markers, and will take more time to eventually change the clinical care delivered to patients with PD."

The composite panel of 10 informative markers assessed in 123 patients with recently diagnosed PD and 106 age-matched neurologically healthy individuals were mainly in the categories of non-motor symptoms, depression, sleep and imaging.

Significant worsening of PD relative to normal aging was seen on part 1 of the Unified Parkinson's Disease Rating Scale (UPDRS) and the Autonomic Scale for Outcomes in Parkinson's Disease (Scopa-AUT). Sleep symptoms worsened on the Epworth Sleepiness Scale and for REM sleep behaviour disorder (RBD) measured by the RBD Screening Questionnaire and by polysomnography. And there was worsening of voxel-based morphometry for cortical grey matter and the hippocampus.

Markers showing relative improvement in PD patients versus healthy individuals were the Nonmotor Symptom Severity Scale (NMSS), and the Beck Depression Inventory and Montgomery-Åsberg Depression Rating Scale.

Commenting on this latter finding in a related editorial, K Ray Chaudhuri (King's College London, UK) says that it is consistent with many studies showing that several non-motor symptoms, including depression, are driven by dopaminergic mechanisms.

"[T]herefore, dopaminergic treatment initiated in the follow-up period would have improved Nonmotor Symptoms Scale (NMSS) and depression scale scores, particularly as the NMSS is sensitive to change", he explains.

The 20 tests that did not show significant and specific progression in PD patients included cognitive assessments and those for cerebrospinal markers previously proposed as biomarkers of PD, including total α-synuclein, amyloid-β 1-42, total and phosphorylated tau protein, and neurofilament light chain proteins.

Chaudhuri says: "The data provide possible insights to the early pathophysiology of PD and inform our changing concepts of symptoms expression in PD. The longitudinal data from this study also underpin the development of a PD biomarker battery rather than single tests".

And adds: "This reflects the multipeptide, multiregional pathology of PD and aligns with attempts to refine the diagnostic criteria for PD."

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