Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

Abstract:

Parkinson’s disease (PD) is a common, progressive, and disabling neurodegenerative movement disorder. Signs and symptoms begin insidiously and overlap with other neurodegenerative conditions, making diagnosis challenging in early disease. Moreover, there are as yet no established biomarkers that will objectively measure disease progression, and this hampers efforts to obtain neuroprotective therapies. At present, diagnosis, measurement of progression, and response to therapeutic intervention rely almost exclusively upon clinical observation. There remains, therefore, a critical need for validated biomarkers. Recent advances in understanding the underlying pathophysiology of PD have aided in identifying strong candidate markers to assist in diagnosis and evaluate progression. Pathways that are disrupted in PD include protein misfolding, mitochondrial dysfunction and increased oxidative stress, dysregulated inflammatory processes, and altered gene expression. For example, α-synuclein is a key contributor to PD pathology, in which misfolded and damaged α-synuclein accumulates in neurons; this is now a leading candidate as a PD biomarker in cerebrospinal fluid. There is also recent evidence that markers of Alzheimer’s disease may be “repurposed” to provide information on PD diagnosis, prognosis, and nonmotor symptoms, including cognitive dysfunction. At the same time, increasingly sophisticated bioinformatics technology allows an unbiased approach to biomarker identification, for example, using proteomic, transcriptomic, and metabolomic analysis. Such generally accessible blood or cerebrospinal fluid tests, if successful, will likely lead to significant improvements in PD diagnosis, management, and research.

Keywords::

• Parkinson’s disease
• neurodegeneration
• α-synuclein
• oxidative stress
• tau

Disclosure

CH receives research funding from the Solomon Family Foundation, the CV Starr Foundation, the Parkinson Disease Foundation, National Institute of Neurological Disorders and Stroke (NINDS), Biogen, and the Michael J Fox Foundation.