Each year in the US, around 90,000 people are diagnosed with Parkinson’s disease.
A study published this week in JAMA Neurology suggests that as many as 20% of these cases may be something else, highlighting the importance of test accuracy.
Parkinson’s disease is a neurodegenerative condition that increasingly compromises an individual’s movement over time. As a build-up of alpha-synuclein proteins causes dopamine-producing neurons in the brain to fail, the body loses its ability to fine-tune motor control, leading to rigidity, tremors, and difficulty maintaining balance.
It’s these clinical symptoms that inform a diagnosis, which, together with a medical history of related signs, determine a prognosis and a course of treatment.
To date, there is no approved blood test, biopsy, or scan that can safely and efficiently identify who is at risk or affected by the pathology, leaving open a strong possibility that, in at least some cases, symptoms are being caused by other factors.
These can include rarer diseases such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA), both of which are often mistaken for Parkinson’s. It can also include other conditions caused by a build-up of alpha-synuclein, known collectively as Lewy body dementia.
This may not just be an issue when it comes to providing suitable treatments. Studies that evaluate Parkinson’s disease are often based on clinically diagnosed patients, which risks including misdiagnosed cases or individuals with other illnesses that could affect their results.
While the fundamental triggers for the disease aren’t fully understood, genes are thought to play a major role, in conjunction with environmental factors that increase the risk of specific neurological damage.
So why not use genes in a diagnosis? Integrating knowledge of genetic factors with clinical evidence is far from straightforward. For one thing, past efforts have been restricted to small, often related groups, typically from a European background.
To untangle potential links between Parkinson’s genes and its pathology across a more diverse population, researchers analyzed brain tissue from more than 3,300 deceased donors who had died between 1985 and 2024 and received some kind of movement-disorder diagnosis while alive.
Just under 750 brains donated from individuals without a diagnosis were used as a control.
Rather than rely on self-reported race and ethnicity data, the researchers determined the ancestry of each sample genetically.
They found that between 10% and 20% of the diagnoses were incorrect. More than one in five cases of MSA were, in fact, another disease, most commonly PSP or Parkinson’s.
Interestingly, having dementia improved the chances that the additional diagnosis of Parkinson’s was accurate.
By comparing genomes, the researchers identified five genes that were previously implicated in neurodegenerative movement disorders. These genetic variants could play a more central role in distinguishing one disorder from another, especially in connection with genetic ancestry.
“Pathological diagnoses differed by ancestry, with South Asian donors more likely to have progressive supranuclear palsy pathology and Ashkenazi Jewish donors more likely to have Lewy body disease, independent of GBA1 and LRRK2 variant status,” the researchers write.
With Parkinson’s disease diagnoses expected to double by the middle of the century, we must develop the right tools to tease apart the specific pathologies underlying similar movement disorders.
This research was published in JAMA Neurology
Source: Scimex
Fact-checked by Bronwyn Thompson
