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.

Biomarkers in Multiple Sclerosis

“…The use of these next-generation technologies has led to the faster search for biomarkers, but the generation of huge datasets is not very meaningful if it is not replicated in an independent study or does not identify already-known disease-related variables. Thus far, data generated by omics studies have not closely paralleled the data collected by focused studies of specific gene transcription and protein changes (Mellick et al 2010). Advances are also needed to simplify the bioinformatics process to analyze and interpret the acquired data, using highthroughput sequencing platforms (Deininger et al 2008;Franck et al 2009).…”

Biomarkers of Parkinson’s disease: Present and future

“…For certain proteins like a-synuclein and DJ-1 the levels in blood are much higher than in CSF suggesting that blood contamination of CSF may be a serious issue [40,41]. A standardization of procedures would help to reduce or eliminate these problems.…”

“…Recent work using CSF and serum from deceased PD patients with a complete pathological assessment shows that the profiling of these cell-free peripheral fluids provides a true reflection of the cellular pathological changes in the diseased tissue [57]. These positive results suggest that the use of platforms that more easily identify groups of analytes that differ between disease and control subjects may advance the search for biomarkers of PD more quickly (however, see [41] for more of a tempered view of large-scale molecular profiling approaches). Despite the enthusiastic acceptance of the technological advances and the collection of multiple large data sets, these approaches have not yet produced any useful clinical biomarkers of PD.…”

Knowing Me, Knowing You: Can a Knowledge of Risk Factors for Alzheimer's Disease Prove Useful in Understanding the Pathogenesis of Parkinson's Disease?

“…In more recent years, technological advances have greatly enhanced the breadth of the questions that can be asked with global analyses such as genome wide association and transcriptomic studies applied to both diseases. However, in general, these genome-scale platforms have only confirmed known risk factors and not identified the novel targets needed to reduce the burden of these diseases [3].…”