Pathophysiology is a term used to describe the changes in the body that happen because of a disease. It helps explain how and why symptoms appear. Instead of just looking at what a disease does, pathophysiology looks at what’s going wrong inside the body to cause those effects. In Parkinson’s, these changes affect how the brain and body work together. This condition doesn’t just affect movement… it can also impact mood, sleep, voice, vision, and digestion.

The role of dopamine & other messengers

To understand Parkinson’s, we need to start with dopamine. Dopamine is a chemical messenger (called a neurotransmitter) that helps control movement and mood. Think of it like the conductor of an orchestra, keeping everything in sync.

In Parkinson’s, the brain cells that make dopamine, especially in a part of the brain called the substantia nigra, start to die off. As these cells disappear, the brain produces less dopamine, and the body struggles to move smoothly. That’s why dopamine replacement therapy is recommended, just like someone who is diabetic needs to replace the insulin their body doesn’t produce anymore, someone with Parkinson’s needs to replace the dopamine.

But dopamine isn’t the only chemical involved. Parkinson’s also affects other neurotransmitters like serotonin, norepinephrine, and acetylcholine, which help regulate mood, sleep, and thinking.

What causes these changes?

Scientists are still learning why Parkinson’s happens. It’s likely caused by a mix of:

  • Genetics – Some people inherit changes in certain genes
  • Environmental factors – Exposure to toxins or pesticides may increase risk
  • Ageing – The risk increases as we get older.

One key player is a protein called alpha-synuclein. In Parkinson’s, this protein clumps together into sticky lumps called Lewy bodies, which damage brain cells. Some researchers believe Parkinson’s may start in the gut or the olfactory bulb (the part of the brain that controls smell), which could explain early symptoms like constipation and loss of smell. There’s also growing evidence that inflammation in the brain (called neuroinflammation) may play a role in how the disease progresses

When do symptoms start?

Parkinson’s symptoms often begin years, even decades, before a diagnosis. Early signs can include:

  • Smaller handwriting
  • Loss of smell
  • Constipation
  • Unexplained pain in the shoulder, back, or hips
  • Changes in mood or motivation to do things you used to love.

As dopamine levels drop by 50% or more, more noticeable symptoms appear, typically leading to a clinical diagnosis. The acronym T.R.A.P. is often used and stands for:

  • Tremor: A resting tremor (shaking hands or twitching fingers) is often one of the first signs in about 70% of people living with Parkinson’s. It usually happens when the hand is still (resting tremor) and may go away with movement. However, another 30% of people have either an active (action tremor) where the hand shakes when moving, or no tremor at all.
  • Rigidity: Muscles become stiff, and movements feel heavy or awkward. You might notice a loss of arm swing or foot dragging.
  • Akinesia (specifically Bradykinesia): Bradykinesia means slowness of movement. Everyday tasks like tying shoes or using a computer mouse become slower and harder.
  • Postural instability: Balance and coordination can be affected, increasing the risk of falls.

Piecing it all together

Diagnosing Parkinson’s can take time. Non-motor symptoms often appear long before movement issues and may not be recognised as part of the condition, especially in younger people aged 20 to 50. There’s no single test or scan to confirm Parkinson’s. Diagnosis usually relies on your GP or neurologist recognising a pattern of symptoms over time and doing a thorough clinical examination.

Hope & progress

There’s currently no cure for Parkinson’s, but research is moving forward. Scientists are learning more about how the condition works, which is helping to develop better treatments. You can participate in clinical trials to help advance research.

Medications, therapies, and lifestyle changes can help manage symptoms and improve quality of life. Understanding the pathophysiology of Parkinson’s helps us see why these treatments matter and why ongoing research is so important.

References

  • Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., … & Lang, A. E. (2017). Parkinson disease. Nature Reviews Disease Primers, 3, 17013.
  • Surmeier, D. J., Obeso, J. A., & Halliday, G. M. (2017). Selective neuronal vulnerability in Parkinson disease. Nature Reviews Neuroscience, 18(2), 101–113.
  • Kalia, L. V., & Lang, A. E. (2015). Parkinson’s disease. The Lancet, 386(9996), 896–912.
  • Braak, H., Del Tredici, K., Rüb, U., de Vos, R. A., Jansen Steur, E. N., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24(2), 197–211.
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