Diagnostic biomarkers for Parkinson's disease at a glance: where are we?

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder whose aetiology remains unclear: degeneration involves several neurotransmission systems, resulting in a heterogeneous disease characterized by motor and non-motor symptoms. PD causes progressive disability that responds only to symptomatic therapies. Future advances include neuroprotective strategies for use in at-risk populations before the clinical onset of disease, hence the continuing need to identify reliable biomarkers that can facilitate the clinical diagnosis of PD. In this evaluative review, we summarize information on potential diagnostic biomarkers for use in the clinical and preclinical stages of PD.

Keywords: Biomarkers; Diagnosis; Parkinson’s disease.

Fig. 1

Parkinson’s disease progression. Non-motor symptoms (NMS) may emerge in a pre-motor or prodromal stage reflecting degeneration in extra-nigral areas before the loss of nigral dopamine neurons. Conversely, the motor symptoms currently required for diagnosis manifest later. From Kalia and Lang (10.1016/S0140-6736(14)61393-3) 2015;386:896–912, copyright (2015) with permission from Elsevier

Fig. 2

An abnormal microbiota in PD (in favour of proinflammatory species) can lead to immune dysregulation and intestinal nervous system inflammation and consequently to a dysfunctional intestinal barrier: α-synuclein pathology can thus spread through the vagal nerve from peripheral autonomic neurons in the gastrointestinal apparatus to the central nervous system. From Perez-Pardo (10.1016/j.ejphar.2017.05.042) 2017 with permission from Elsevier

Fig. 3

7-Tesla magnetic resonance imaging scan (MRI) scan showing mesencephalic anatomy in a control (C) and a patient with Parkinson’s disease (PD). Nigrosome-1 (white arrowheads) appears as a hyperintense pocket (due to a low iron content) in the control subject whereas it is not visible in the PD patient, in whom shape analysis shows undulation in the anterolateral perimeter of the subthalamic nucleus (arrow). From Lehéricy et al. (10.1002/mds.26043), 2014 with permission from John Wiley and Sons

Fig. 4

Genetic risk factors for Parkinson’s disease. Parkinson’s disease (PD) has a multifactorial genesis and, although only about 10% of patients have a family history, at least 30% of the risk of PD developing depends on genetic factors, which differ in strength and allele frequencies. The size of the bubbles corresponds to population; the size of the rings corresponds to allele frequencies; inheritance is shown by colours (blue = dominant, yellow = recessive, green = risk loci). From Gasser (10.3233/JPD-140507) 2015 with permission of IOS Press