3 blood biomarkers might identify Parkinson’s, atypical parkinsonism

Shared symptoms complicate efforts to accurately diagnose patients

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Certain biomarkers in the blood may help doctors in determining whether a person has Parkinson’s disease or atypical parkinsonism, both of which show similar symptoms, a study reported.

Three biomarkers — neurofilament light chain (NfL) and malondialdehyde (MDA), particularly, but also 24S-hydroxycholesterol (24S-HC) — were found at significantly different levels in people with Parkinson’s and those with related conditions.

Each marker correlated to some degree with motor and/or clinical symptoms in patients.

“Considering the current challenges in this field, combination of biomarkers with clinical (e.g., gait disorders), genetic, and radiological [imaging] data could thus help to improve the ability to diagnose, phenotype [characterize] and ultimately propose personalized therapeutics and rehabilitation for patients,” the researchers wrote.

The study, “Neurodegeneration, oxidative stress and lipid metabolism plasma biomarkers to differentiate Parkinson’s disease from atypical parkinsonian syndromes,” was published in Revue Neurologique.

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Diagnosing Parkinson’s disease, atypical parkinsonism challenging

Parkinsonism is an umbrella term referring to a set of symptoms such as slow movements, rigidity or stiffness, tremors, and mobility issues.

While they are typical Parkinson’s symptoms, they also characterize a range of other brain conditions known collectively as atypical parkinsonian syndromes or APS. Such conditions include multiple system atrophy, corticobasal ganglionic degeneration, dementia with Lewy bodies, and progressive supranuclear palsy.

APS usually has a poorer prognosis and a worse response to treatment than Parkinson’s.

Criteria for diagnosing Parkinson’s are distinct from those for APS. But with many shared symptoms, it can be hard to doctors to differentiate between the two. The rate of misdiagnoses ranges from 15% to 38%, the researchers noted.

Blood or spinal fluid biomarkers could serve as a possible way of distinguishing Parkinson’s from APS, but more work is needed to determine those most likely to best do so.

Researchers in France looked at blood levels of three biomarkers believed to have potential for differentiating between the conditions among 32 Parkinson’s patients and 15 adults with APS seen at a clinic in Dijon.

Parkinson’s patients, with an average age of 58.5, had a mean disease duration of 4.75 years; APS patients, with an average age of 70.5, had a mean disease duration of 4.2 years. APS patients had more severe motor impairments than did Parkinson’s patients.

Researchers first looked at levels of NfL, a biomarker of nerve damage and neurodegeneration. NfL levels previously have been shown to differ between Parkinson’s and APS patients.

Significant differences by condition seen in biomarkers’ blood levels

Here, NfL levels were seen to be about twice as high in the APS group relative to the Parkinson’s group, a significant difference.

Similarly, MDA levels were significantly elevated in APS patients compared with Parkinson’s patients. MDA is a marker of oxidative stress, a type of cellular damage that arises when there is an imbalance in toxic oxidative molecules and antioxidants available to combat them. This process has been implicated in Parkinson’s-associated neurodegeneration.

24S-hydroxycholesterol (24S-HC), a marker of lipid (fat) metabolism, is also dysregulated in Parkinson’s and thought to contribute to nerve damage.

In contrast to the other biomarkers, 24S-HC levels were significantly lower in the APS group than in the Parkinson’s group.

All three biomarkers were able to distinguish Parkinson’s from APS patients, while NfL and MDA, particularly, showed “high diagnostic accuracy,” the researchers wrote.

The likelihood of an APS diagnosis rose significantly with NfL levels at or above 47.2 picograms per milliliter (mL), MDA levels at or above 23.628 nanomoles per mL, and 24S-HC levels at or below 33.4 picomoles per mL.

Moreover, levels exceeding the cutoff values for both NfL and MDA were associated with an even higher likelihood of an APS diagnosis, raising the odds by more than 30 times relative to people whose values were below the cutoff.

Severity of motor and cognitive symptoms link with NfL, MDA levels

The combination of NfL and 24S-HC, MDA and 24S-HC, or all three markers combined also “systematically classified patients in the APS group,” the team wrote.

Levels of each biomarker correlated to some degree with patients’ motor and cognitive function. Particularly, higher NfL and MDA levels associated with motor and cognitive symptom severity, whereas lower 24S-HC values linked to poorer motor skills but did not associate with cognitive abilities.

“Taken together, these results suggest a close relationship between oxidative stress, neurodegeneration, and clinical impairment,” the researchers wrote.

Study limitations included its limited number of patients and lack of long-term data, highlighting the need for larger studies — and in patient groups within three years of diagnosis — to confirm the findings and allow for an early distinction.

“Nevertheless, our data suggest that all three biomarkers, and particularly MDA and NFL, could be helpful to differentiate [Parkinson’s] from APS,” the team concluded.