Diagnostic Biomarkers of Parkinson's Disease

Introduction

Neurodegenerative disease is a pathology that affects the central nervous system and causing damage or permanently destroying neurons. Neurons are cells incapable of reproducing and cannot be replaced. Damage or destruction leads to a failure in the functions they perform within the nervous system, which is made up of the brain and spinal cord. The treatment of these diseases is aimed at improving mobility and relieving symptoms of pain. In short, the purpose of treatment is to prolong the life of the patient whenever possible and improve their quality of life and that of the people around them.

Currently, emerging approaches are applied, such as the use of biological markers (biomarkers) and, from these, carrying out the diagnosis or monitoring of the evolution of this pathology. Knowledge of the pathophysiological processes that produce and progress with this disease is essential for the search for biomarkers that help in its diagnosis, preferably early, and once diagnosed, to follow the process and know the prognosis of the disease.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimers disease (Hirtz et al., 2007). It is a chronic and progressive disorder that is estimated to affect over 4 million people worldwide (Dorsey et al., 2007), although it is likely that this number is underestimated (Van Den Eeden et al., 2003). It is a neurodegenerative disease whose essential pathological substrate is the degeneration of dopaminergic neurons of the pars compacta (SNpc) ofthe substantia nigra (SN) “black substance”. Consequently, there is a loss of dopaminergic innervation in the striatum that causes the cardinal signs of the disease: resting tremor, rigidity, and bradykinesia (Fahnet al., 1971).The symptoms and signs of PD usually do not develop until 70–80% of dopaminergic neurons have already been lost(El-Agnaf et al., 2006). Treatment with levodopa (Birkmayer and Hornykiewicz, 1961; Cotzias et al., 1968; Hornykiewicz, 1974) or dopaminergic agonists produces an improvement in classic motor signs, although their chronic use is associated with complications such as dyskinesias, motor, and non-motor fluctuations and impulse control disorder (ICD). As the disease progresses, the cardinal signs, which are initially usually confined to one side of the body, become progressively generalized and the so-called axial signs appear, such as postural instability or gait blockages.

In addition to these manifestations, PD is characterized by another group of signs and symptoms called “non-motor symptoms”. Although they may be present from thebeginning and even before the motor manifestations appear, they are more frequent in late stages (Rodriguez-Oroz et al., 2009a).These include autonomic nervous system disturbances (orthostatic hypotension, poor sphincter control, erectile dysfunction, sweating disturbances), sleep disturbances (insomnia, daytime hypersomnia,) sleep behavior motor disorder (RBD) (Chaudhuri et al., 2006; Jankovic et al., 2008;),psychiatric disorders (anxiety, depression, apathy, hallucinations, delusions), alterations of the gastrointestinal tract (dysphagia, slowing of intestinal transit, constipation) and cognitive deterioration. Although initially this group of manifestations was overshadowed, probably due to the need for medical research to control the motor manifestations of the disease, in recent years they have gained special relevance. Today, it is widely accepted that these manifestations produce as much or more deterioration in quality of life than motor aspects (Simuni and Sethi, 2008) and, therefore, research in this field has been extremely prolific in recent years. Especially relevant is cognitive impairment which, although initially, it does not usually interfere with daily functionality, progresses to dementia in a significant proportion of patients.