Signs of Parkinson’s may be visible long before diagnosis

Using PET scans to track the VMAT2 protein may yield clues decades earlier

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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It may be possible to spot telltale signs of Parkinson’s disease on positron emission tomography (PET) scans as early as 20 to 30 years before symptoms become evident and a definite clinical diagnosis can be made, a study suggests.

PET scans that track a protein called vesicular monoamine transporter 2 (VMAT2), whose levels reflect the loss of neurons (nerve cells) in the brain of people with Parkinson’s, also were able to monitor disease progression over a two-year window.

“Parkinson’s disease is very hard to diagnose until symptoms are obvious, by which time up to 85 per cent of the brain’s neurons that control motor coordination have been destroyed,” Kevin Barnham, PhD, one of the researchers in the study, said in a press release.

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An illustration shows a close-up view of neurons.

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Barnham, who’s a professor at The Florey Institute in Melbourne, Australia, added that “at that point, many treatments are likely to be ineffective. Our long-term goal is to find a way to detect the disease much earlier and treat people before the damage is done.”

The study, “Utilizing 18F-AV-133 VMAT2 PET Imaging to Monitor Progressive Nigrostriatal Degeneration in Parkinson Disease,” was published in the journal Neurology.

It can be challenging to diagnose Parkinson’s because its symptoms usually develop gradually over many years and there isn’t a specific test that can conclusively diagnose the disease.

Subtle early signs may be present years before symptoms become evident, and identifying them could help to screen for people at risk, monitor disease progression, and measure response to treatment.

PET is an imaging technique that works by detecting the radiation given off by a tracer injected into the bloodstream, as the tracer travels to and collects in different parts of the body.

The 18F-AV-133 PET tracer

Teaming up with other researchers in Australia and the U.S., Barnham sought to assess whether 18F-AV-133 — a PET tracer designed to bind to VMAT2 — was sensitive enough to monitor disease progression over a two-year window.

VMAT2 is involved in the uptake of dopamine into neurons, and a reduction of VMAT2 reflects the loss of dopamine-producing neurons in the brain’s nigrostriatal pathway — a main hallmark of Parkinson’s. Dopamine is a chemical messenger that nerve cells use to communicate.

The study included 26 people with Parkinson’s, 12 healthy individuals, and 11 people with rapid eye movement behavior disorder (RBD), a sleep disturbance that often precedes Parkinson’s. All were scanned twice 26 months (about two years) apart.

Over the two-year window, there were no significant changes in clinical symptoms in any of the participants according to currently available assessments for Parkinson’s, including the evaluation of motor symptoms.

By contrast, the signal intensity of the 18F-AV-133 tracer, which shows up in areas of the brain where VMAT2 is active, declined in the caudate nucleus and the anterior and posterior putamen. These three areas are part of the nigrostriatal pathway.

More possible signs of Parkinson’s

The PET scans also detected a loss of dopamine-producing neurons in the posterior putamen of people with RBD versus healthy individuals, suggesting 18F-AV-133 may be a more sensitive way to monitor disease progression than currently available assessments.

Using mathematical models, the researchers estimated that neurodegeneration leading up to Parkinson’s may occur slowly over the course of about 33 years. In the posterior putamen, neurodegeneration may begin 10.5 years before it is visible on PET scans.

It may take a 6.5 more years until the first symptoms emerge, and another three years until a definite clinical diagnosis can be made. “Trajectory models propose that there is nigrostriatal degeneration occurring for 20 years before clinical diagnosis,” the researchers wrote.

“Over a two-year period, 18F-AV-133 VMAT2 PET was able to detect progression of nigrostriatal degeneration in participants with [Parkinson’s] and represents a sensitive tool to identify individuals at risk of progression,” the researchers concluded.

“These data demonstrate that VMAT2 PET provides a sensitive measure to monitor neurodegenerative progression of [Parkinson’s,] which has implications for [Parkinson’s] diagnostics and subsequently clinical trial patient stratification and monitoring,” they added.