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JUNE 19, 2019

Study reveals roots of Parkinson's in the brain

by King's College London

Brain imaging showing loss in serotonin function as Parkinson's disease progresses. Red/yellow ar…

Researchers from King's College London have uncovered the earliest signs of Parkinson's
disease in the brain, many years before patients show any symptoms. The results, published in
The Lancet Neurology, challenge the traditional view of the disease and could potentially lead
to screening tools for identifying people at greatest risk.

Parkinson's disease is the second most common

neurodegenerative disorder, after Alzheimer's
disease. The disease is characterised by
movement and cognitive problems but is known to
become established in the brain a long time before
patients are diagnosed. Studying the crucial early
stages of the disease, when treatment could
potentially slow its progress, is a huge challenge.
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The new study, funded by the Lily Safra
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Discover Something New. Foundation, provides the Prst evidence of a central
role for the brain chemical serotonin in the very
earliest stages of Parkinson's. The results suggest changes to the serotonin system could act
as a key early warning signal for the disease.

Chief investigator Professor Marios Politis, Lily Safra Professor of Neurology & Neuroimaging
at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), says: 'Parkinson's disease
has traditionally been thought of as occurring due to damage in the dopamine system, but we
show that changes to the serotonin system come Prst, occurring many years before patients
begin to show symptoms. Our results suggest that early detection of changes in the serotonin
system could open doors to the development of new therapies to slow, and ultimately prevent,
progression of Parkinson's disease.'

Brain imaging showing loss in serotonin function as Parkinson's disease progresses. Blue/black ar…

People with Parkinson's disease have build-ups of the protein α-synuclein in the brain. While
there is no clear cause for most people, a minority of cases are caused by genetic mutations.
People with mutations in the α-synuclein (SNCA) gene are extremely rare but are almost
certain to develop Parkinson's disease during their lifetime, making them ideal for studying the
train of biological events that leads to Parkinson's disease.

The SNCA genetic mutation originates in villages in the northern Peloponnese in Greece and
can also be found in people who migrated to nearby regions in Italy. Over two years, the
researchers identiPed 14 people with the SNCA gene mutation from Greece and Italy and [ew
them to London for brain imaging and clinical assessments. Half of the participants had not
begun to show any symptoms of Parkinson's.

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Data from the 14 people with SNCA gene mutations were compared with 65 patients with non-
genetic Parkinson's disease and 25 healthy volunteers. The researchers found that the
serotonin system starts to malfunction in people with Parkinson's well before symptoms
affecting movement occur, and before the Prst changes in the dopamine system.

First author Heather Wilson, from the IoPPN, says: 'We found that serotonin function was an
excellent marker for how advanced Parkinson's disease has become. Crucially, we found
detectable changes to the serotonin system among patients who were not yet diagnosed.
Therefore, brain imaging of the serotonin system could become a valuable tool to detect
individuals at risk for Parkinson's disease, monitor their progression and help with the
development of new treatments.'

Brain imaging was carried out using PET scans which are expensive and di_cult to carry out.
The researchers say further work is required to develop the scanning techniques in order to
make them more affordable and straightforward for use as screening tools.

More information: Neurology (2019). DOI: 10.1016/S1474-4422(19)30140-1

Journal information: Neurology , Lancet Neurology

Provided by King's College London

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