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Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease. It typically manifests later in life and is characterized by tremors and a shuffling gait. Findings from a recent study suggest that there are two subtypes of the disease — one originating in the brain and the other arising in the peripheral nerves outside the brain.

Parkinson’s disease is associated with the death of dopamine-producing neurons and the build-up of a misfolded protein, known as alpha-synuclein, in the brain. Diagnosis coincides with the onset of motor symptoms, which occurs when fifty percent of dopaminergic neurons are lost. However, a subset of people experience non-motor symptoms, such as constipation, depression, and sleep problems, several years before diagnosis.

Previous research suggests that the disorder arises in the brain, while other data point to its origins in the peripheral nervous system. The current study used imaging techniques to investigate whether these two lines of evidence were pointing to two disease subtypes: brain-first and body-first.

REM sleep behavior disorder (RBD) is characterized by vivid dreams and excessive movements during the rapid eye movement phase of sleep. Since RBD precedes brain changes associated with various neurological disorders, the authors of the study hypothesized it was a marker for a body-first subtype.The case-control study involved 37 people with suspected Parkinson’s disease between the ages of 50 and 85 years, and 22 people with RBD of unknown cause. The authors used video-polysomnography to divide participants into those with RBD and those without the condition. They scanned the participants' brains, along with nerves in their colons and hearts.

In some people the scans revealed that brain degeneration occurred before the colon and heart were affected, while in other people, peripheral nerves were involved before the brain’s dopaminergic cells were affected. Furthermore, the researchers observed that RBD is predictive of the body-first subtype.

These findings suggest that two subtypes of the disease exist, one originating in the brain, and one beginning in the nerves of the periphery. This hypothesis, if confirmed, has implications for the treatment of this devastating disease.

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