CSF Biomarkers May Distinguish Parkinson’s, Atypical Parkinsonism

Researchers looked for studies that reported on differences in levels of 18 CSF biomarkers

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Levels of alpha-synuclein, beta-amyloid, and neurofilament light chain (NfL) in the cerebrospinal fluid (CSF) that surrounds the brain and the spinal cord can help identify Parkinson’s disease and distinguish it from atypical parkinsonism, according to a review study.

The study, “A meta-analysis of the diagnostic utility of biomarkers in cerebrospinal fluid in Parkinson’s disease,” was published in npj Parkinson’s Disease.

There’s currently no single test to make a diagnosis of Parkinson’s, meaning it may take numerous steps, from collecting a complete medical history to performing a detailed physical examination or getting additional tests. The fact that other neurodegenerative disorders share some Parkinson’s symptoms can make a diagnosis even harder.

These conditions, called atypical parkinsonism syndromes, include multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and cortical basal degeneration (CBD).

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Changes in Protein Structure May Act as Parkinson’s Biomarkers

As such, “identifying diagnostic and prognostic biomarkers of [Parkinson’s disease] is important in the area of neurodegenerative disorders,” the researchers wrote.

The CSF flows in and around the brain and the spinal cord and can be a window into their workings. Therefore, “CSF biomarkers can better reflect disease stages compared with blood or other biomarkers,” the researchers wrote.

Distinguishing CSF biomarkers

To find out which CSF biomarkers may be used to diagnose or distinguish Parkinson’s from atypical parkinsonism, researchers in China reviewed published studies from January 1, 1970 to July 1, 2022 that reported findings on the subject.

The researchers looked for studies that reported on differences in the levels of 18 CSF biomarkers between Parkinson’s patients and either healthy people (or those with other neurological disorders) or those with atypical parkinsonism.

Evaluated biomarkers included proteins such as alpha-synuclein, beta-amyloid, and tau that are known to aggregate and accumulate to toxic levels in Parkinson’s and other neurodegenerative diseases. Markers of neurodegeneration, neuroinflammation, and proteins involved in oxidative stress, a type of cellular damage implicated in neurodegenerative diseases, were also included.

Of a total of 1,175 studies assessed for eligibility, 123 were included in the meta-analysis. The studies involved 11,688 Parkinson’s patients, 859 people with MSA, 708 DLB patients, 327 people with PSP, 32 CBD patients, and 6,735 controls (5,757 healthy people and 978 with other neurology disorders).

Results showed that, compared with controls, Parkinson’s patients had lower levels of total alpha-synuclein, beta-amyloid, tau protein, YKL-40 (a neuroinflammation marker), and DJ-1 and zinc, which typically work against oxidative stress.

Clumps of beta-amyloid and tau protein are usually found with Alzheimer’s disease, another neurodegenerative disease and the most common cause of dementia.

In turn, the levels of the abnormal forms of alpha-synuclein (oligomeric and phosphorylated) that generate toxic clumps in Parkinson’s were higher in the CSF of people with the neurodegenerative disease than in controls.

Total alpha-synuclein worked well to distinguish Parkinson’s patients from controls, with a sensitivity of 85% (true-positive rate) and a specificity of 75% (true-negative rate).

The researchers did find that lower levels of NfL, a biomarker of nerve cell damage, could help distinguish Parkinson’s from atypical parkinsonism syndromes, except for DLB.

However, beta-amyloid “could bridge the gap,” the researchers wrote, with it detected at higher levels in the CSF of people with Parkinson’s than with DLB.

“Based on the diagnostic utility and the included number of studies, we believe that a combination of [total alpha-synuclein], NFL, and [beta-amyloid] could be helpful for the diagnosis and differential diagnosis of [Parkinson’s disease],” the researchers wrote. “Further investigation of the use of combined CSF biomarkers in PD is warranted and may be improved using detailed demographics and clinical variables.”

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