Parkinson’s disease

What happens in the brain

Parkinson’s disease involves the loss of dopamine-producing neurons in a small midbrain region called the substantia nigra, along with the accumulation of misfolded alpha-synuclein protein into clumps called Lewy bodies. The movement symptoms (tremor, slowness, stiffness, balance problems) are the most visible, but the disease also affects sleep, mood, digestion, blood pressure regulation, smell and, in many people, cognition.

The World Health Organization reported more than 8.5 million people living with Parkinson’s in 2019, with prevalence having doubled over the preceding 25 years, and notes that it is the fastest-growing neurological disorder in terms of disability and death.

A disease of clearance?

Alpha-synuclein, like amyloid, is a protein the brain must dispose of, and glymphatic transport of alpha-synuclein has been demonstrated in animal models. Sleep disturbance, including REM sleep behaviour disorder, is one of the earliest signs of Parkinson’s, sometimes preceding motor symptoms by years, which fits a picture in which the brain’s night-time clearance is compromised early.

Mitochondria are also central to Parkinson’s. Several of the genes that cause inherited forms of the disease, including PINK1 and Parkin, control how cells identify and recycle damaged mitochondria, and dopamine neurons are unusually energy-hungry and vulnerable to that failure. Imaging studies of fluid movement in the brains of people with Parkinson’s are an active research area, and early results point toward impaired clearance alongside the better-known cellular changes.

What can be done today

Dopamine-replacement medication, deep brain stimulation and, increasingly, exercise programmes are the mainstays of care. Numerous disease-modifying approaches are in trials. The Michael J. Fox Foundation’s video on this page offers a clear five-minute overview, and anyone with symptoms should see a neurologist. This page is educational background and not medical advice.

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