Biomarkers in Parkinson's Disease

An Update

Alexander Shtilbans; Claire Henchcliffe

Disclosures

Curr Opin Neurol. 2012;25(4):460-465. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: This review article is focused upon the most recent biomarker studies of Parkinson's disease. It provides an update on promising areas of biomarker research in a rapidly expanding field, and discusses future directions that might lead to successful development of Parkinson's disease biomarkers.
Recent findings: Studies of molecular-genetic and biochemical biomarkers of Parkinson's disease have not only targeted hypothesis-driven measures of specific substrates involved in processes such as protein misprocessing, but also have made use of sophisticated analyses such as transcriptomic, proteomic, and metabolomic approaches. Whereas none of these are yet established as Parkinson's disease biomarkers, brain imaging using the123I-ioflupane ligand with single-photon emission computed tomography was recently approved in the United States to aid in Parkinson's disease diagnosis, and research on other imaging modalities is ongoing. Neurophysiological tests are also being adapted for biomarker research, and we review recent promising data.
Summary: The search for effective biomarkers for diagnosis and surveillance of Parkinson's disease continues. A battery of biomarkers comprising different modalities might be required to address clinical needs in this complex disorder. Critically, collaborative efforts including centralized tissue repository and clinical research infrastructure that are being organized will advance this field further.

Introduction

Parkinson's disease is the second most common neurodegenerative disease, estimated to occur in approximately 1% of individuals >60 years of age, with 4.1–4.6 million affected worldwide,[1] a number predicted to more than double by 2030, as populations age.[2] Despite rigorous research efforts, patient management and clinical research are still hampered by suboptimal methods for diagnosis, refining prognosis, predicting individual response to therapeutic interventions, and tracking disease progression. Validated biomarkers with a high degree of sensitivity and specificity are, therefore, critically needed. In fact, there are still no reliable biomarkers to test potentially neuroprotective interventions, and this is a major roadblock to clinical trial design. Moreover, if potential neuroprotective interventions are identified, it will be important to have biomarkers to provide meaningful risk-stratification in asymptomatic individuals in order to address potential preventive approaches. Additionally, with the development of biologically informed therapies, such as for mitochondrial dysfunction[3] or specific kinase activity,[4] it will be important to obtain biomarkers that will identify endophenotypes, in order to provide a more precise rationale for defining appropriate study populations.

The search for such biomarkers is on. For example, neuroimaging techniques that examine ligand uptake reflecting nigrostriatal tract integrity are now available in the clinical and research realms, and other imaging modalities are in active testing. Recent advances have also provided several promising molecular biomarker candidates based upon examination of body fluids such as blood, cerebrospinal fluid (CSF), or saliva. However, validation will require access to a large quantity of tissue samples, ideally longitudinally. Collaboration between research centers will be needed to coordinate efforts, and for this reason, organized initiatives such as the Parkinson Progression Marker Initiative (PPMI)[5] and Longitudinal and Biomarker Study-Parkinson's disease[6] will likely prove an important means of advancing studies. In this review, we focus upon recently emerging data, and how far along we are in attaining the goals enumerated above (previous studies are the subject of recent reviews).[7–9]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....