Parkinson's Disease
Let's use Medisearch to give us a brief overview of Parkinson's disease (PD):
Now let's dive deeper into Parkinson's disease. What are the symptoms, pathology and genetics of Parkinson's disease?
Symptoms of Parkinson's Disease
Parkinson's Disease is a neurodegenerative hypokinetic disease, where 'hypokinetic' refers to the diminished ability to move.
Therefore, the most common symptoms involve slow movement, stiff and inflexible muscles and tremors [1,2].
- Tremors: Uncontrolled shaking, especially in the hands.
- Bradykinesia: Slowed movements and difficulty initiating movements.
- Muscle stiffness: Feeling stiff or rigid on one or both sides of the body.
- Balance and coordination problems: Trouble with balance, coordination, and increased risk of falls. Individuals suffering from PD often have a snooped posture.
- Changes in walking: Altered gait, shuffling steps, and difficulty with initiating or stopping movements.
Additionally, PD patients can experience a variety of non-motor symptoms, as the Lewy body pathology is present in multiple brain regions.
Non-motor symptoms include memory problems, loss of smell, constipation, dysphagia, urinary problems, visual disturbances but also sleep disturbances, depression, anxiety and apathy [3]. Weight loss is also often observed in PD patients. Additionally, peripheral neuropathy has also been observed in PD patients.
Interestingly, a study examining patients with Parkinson's disease found that the non-motor symptoms, such as apathy or excessive sleepiness during the daytime, or sleep problems and constipation are much more frequent in patients with Parkinson's disease before their diagnosis than in healthy controls [4].
This suggests that there are processes occurring in the brain before the motor symptoms manifest. The innocent-looking non-motor symptoms may already be PD, but the disease is diagnosed later.
Pathology of Parkinson's Disease
What Causes Parkinson's Disease?
Parkinson's disease is caused by the loss of neurons in a brain region called the substatia nigra.
Additionally, in Parkinson's disease, we observe the accumulation of a protein called alpha-synuclein [5]. The aggregated and accumulated alpha-synuclein forms so-called Lewy bodies.
These are found in the cytoplasm of neurons in multiple brain regions.
Interestingly, the presence of Lewy bodies is not PD-specific and can be seen in other neurodegenerative diseases such as Dementia with Lewy bodies or even Alzheimer’s disease [6].
While various types of neurons, including glutamatergic, cholinergic, GABAergic, tryptaminergic, noradrenergic, and adrenergic, are influenced by the pathological hallmarks of Parkinson's disease, it is the degeneration of dopaminergic neurons in the striatum and substantia nigra that strongly correlates with the motor impairments observed in affected individuals.
What Are Dopaminergic Neurons?
Dopaminergic neurons are a type of nerve cells in the brain that produce and release dopamine, a neurotransmitter that plays a crucial role in several brain functions.
They are found in several areas of the brain, including the substantia nigra and the ventral tegmental area.
Some of the functions of dopaminergic neurons include movement control, mood regulation, addiction, and stress response.
The loss of these neurons can also affect diseases other than PD, such as schizophrenia or bipolar disorder. The exact role of dopaminergic neurons in these diseases is perhaps a topic for another blog post, but try using MediSearch to examine this connection deeper.
What Causes The Loss of Dopaminergic Neurons in Parkinson's Disease?
A natural question to ask is what causes the loss of dopaminergic neurons in PD. It turns out, that the exact mechanism is not fully understood.
The answer to this question is crucial to understanding why Parkinson's disease occurs, and this highlights the need for further research in this area.
Let's use MediSearch to understand the causes behind the loss of dopaminergic neurons in PD:
Stages of Parkinson's Disease
As we mentioned, the motor symptoms of Parkinson's disease are strongly correlated with the loss of dopaminergic neurons. In fact, when the motor symptoms begin to appear, almost around 80% of the dopaminergic neurons in the substantia nigra and system are already lost [7].
Braak et al. determined different stages of Parkinson's disease [8].
They found out that the pathology first arises in the brain regions called medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. This aligns with the studies suggesting that non-motor symptoms occur prior to the onset of motor symptoms. Therefore the pathology appearing in these brain regions can cause non-motor symptoms.
As the disease is progressing, and the pathology is spreading, alpha-synuclein appears in the substantia nigra and that’s when the motor symptoms appear as well. The disease can be separated into distinct stages, which we explain in our blog about the 5 stages of Parkinson's disease.
New Insights in Parkinson's Disease Pathology Research
The pathology of PD is still being investigated, and new insights are being revealed.
For example, a study examining Parkinson's disease in mice found a surprising connection between the underlying mechanism of PD and the gut.
Intriguingly, they found that the main contributor to Parkinson's disease, the alpha-synuclein, travels from the brain to the gut in PD mice models [9].
In fact, this is part of a wider trend in neurological research. Scientists are slowly uncovering evidence that our gut may influence other processes in our body, and may contribute to diseases that seem completely unrelated, such as depression or ALS.
Genetics of Parkinson's Disease
Typically, Parkinson's disease happens sporadically, with no previous familial history. However, Parkinson's disease can be inherited - around 5-10% of all PD cases are due to a heritable form of PD.
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Diagnosis of Parkinson's Disease
The diagnosis of many neurodegenerative diseases is tricky, and Parkinson's is no exception.
Primarily, the diagnosis revolves around the clinical symptoms and their identification [10].
Usually, it is only possible to diagnose the disease already when the symptoms are already manifesting [11].
To supplement the clinical diagnosis, neuroimaging of the brain is also used.
It supports or disapproves the clinical diagnosis, assesses the disease progression and can help with evaluation of the effect of treatment.
Such techniques include Magnetic resonance imaging (MRI), Positron emission tomography (PET) and Single photon emission computed tomography (SPECT).
Unfortunately, in terms of biomarkers, neither cerebrospinal fluid nor blood fluid biomarkers have yet not been proven to be effective in PD diagnosis [12]. Therefore, further research in this area is needed.
Treatment of Parkinson's Disease
The degeneration of dopaminergic neurons leads to the clinical manifestation of the motor symptoms in Parkinson's disease.
Therefore, a dopamine precursor L-DOPA was the first proposed treatment for Parkinson's disease. It is effective in managing the motor symptoms of the disease, however, after a while it shows a decrease in efficiency and evokes side effects [13].
That is why there are also other treatment medications such as monoamine oxidase type B (MAOB) inhibitors, Catecgol-O-methyltransferase ( COMT) inhibitors and dopamine agonists.
Dopamine agonists mimic the effects of dopamine in the brain.
MAOB inhibitors inhibit the breakdown of dopamine in the brain, increasing its availability and COMT inhibitors which are usually used with L-DOPA prolong the effects of levodopa by inhibiting its breakdown.
Non-pharmacological treatment of PD includes deep brain stimulation. Deep brain stimulation involves surgical implantation of electrodes which stimulate subcortical structures within the brain.
It is effective and reduces the motor symptoms of the disease especially when the side effects of L-DOPA are problematic [14].
Excitingly, a recent advancement in the treatment of Parkinson's disease symptoms has been made. A spinal cord implant was found to be effective in improving the movement of a patient with Parkinson's disease. This provides hope for more advanced treatment of the disease, but more research is needed [15].
Conclusion
Parkinson's disease is a neurodegenerative disorder marked by the loss of dopaminergic neurons and the accumulation of alpha-synuclein.
Genetic factors contribute to a heritable form in a subset of cases.
Clinical manifestations encompass motor and non-motor symptoms, posing diagnostic challenges that current biomarkers struggle to address.
While traditional treatments like L-DOPA manage motor symptoms, they exhibit limitations. Deep brain stimulation emerges as a promising alternative, alleviating symptoms and offering hope for advanced cases.
Ongoing research explores new treatments and potential biomarkers for early Parkinson's disease detection, promising a brighter outlook for comprehensive management and improved quality of life for those affected.