Exploiting the potential of molecular profiling in Parkinson’s disease: current practice and future probabilities

Abstract

Parkinson’s disease (PD) is a common, heterogeneous syndrome diagnosed clinically by the presence of classical neurological symptoms and the absence of ‘red flags’ that suggest alternative secondary parkinsonian disorders. Neuropathologically, nigrostriatal loss and the presence of proteinaceous inclusions (Lewy bodies) confirm the diagnosis. For PD, molecular profiling promises much but is yet to deliver in terms of breakthroughs for identifying at-risk individuals, detecting disease at early stages, improving diagnostic certainty, prognosticating future outcomes or providing surrogate markers of therapeutic efficacy. Recent, large-scale omics studies, driven by technological advances, have generated terabytes of data but not yet met the goal of developing biomarkers suitable for clinical use in PD. In this article we critically evaluate the recent literature to identify the key roadblocks and realistic opportunities facing researchers interested in utilizing molecular profiling in the clinic to improve the diagnosis and treatment of PD.

Keywords::

• biomarkers
• genomic
• metabolomic
• molecular profiling
• Parkinson’s disease
• proteomic
• transcriptomic

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

While a combination of six cerebrospinal fluid protein analytes was able to retrospectively discriminate between cases and controls with reasonable success in the study of Zhang and colleagues, none of these proteins was identified in the study of Sinha et al.

Apo: Apolipoprotein; BDNF: Brain-derived neurotrophic factor; VDBP: Vitamin D-binding protein.

This is a subgroup of 57 proteins uncovered by stepwise discriminate analysis as significant contributors to the discrimination between PD and control samples in a prospective investigation of 62 PD and 30 control subjects.

Identified by Goldknopf and colleagues [88].

Apo: Apolipoprotein; LBD: Lewy body dementia; PD: Parkinson’s disease.

^†Identified by Ahmed and colleagues as being associated with Parkinson’s disease [104].