Parkinson's Disease: Clinical Manifestations and Risk Factors

Introduction

Parkinson's disease is primarily caused by a progressive degeneration of dopamine neurons in the brain, dopamine being a neurotransmitter involved in the control of many functions such as voluntary movements, cognition, motivation, and affect other functions. This neuronal death is associated with three essential phenomena: Firstly an accumulation of clusters called Lewy bodies, made up largely of the protein α-synuclein, secondly abnormal activity of the mitochondria, which are the “powerhouses” of cells; and thirdly inflammation of brain tissue, which would be linked to several types of immune cells: microglial cells of innate immunity, and T lymphocytes of adaptive immunity.

α-synuclein is a naturally occurring protein in humans. In people with Parkinson's disease, it acquires an abnormal three-dimensional structure that promotes a phenomenon of aggregation, harmful to cell function. It has been shown, in animals, that “sick” α-synuclein carries the necessary and sufficient information to trigger and advance the disease: an abnormal α-synuclein can trigger the transformation of α-synuclein whose structure is normal in “diseased” proteins. The anomaly thus spreads step by step within a neuron, then from one neuron to another.

The dopaminergic neurons of the nigrostriatal region of the brain (black substance), in charge of the coordination of movements, are those which degenerate preferentially and massively: this explains why Parkinson's disease often manifests itself first by motor symptoms. But the disease is not restricted to cells of the substantia nigra. Indeed, the presence of Lewy bodies – or synucleinopathy – is observed in other cerebral dopaminergic neurons, in particular at the level of the olfactory bulb or the cortico-mesolimbic pathways, as well as in the neurons of the intestine (enteric nervous system). Moreover, as the disease progresses, neuronal populations associated with other neurotransmitters (serotonin, acetylcholine or norepinephrine) are also affected by synucleinopathy and neuronal degeneration.

Parkinson’s disease (PD)ranks second among the most prevalent neurodegenerative diseases, and first in disorders that affect movement. The prevalence of PD is reported to be approximately 1% in people 60 years of age and older and increases to 1% to 3% in the 80-plus age group (De Lau et al., 2006; Driver et al., 2009)