Nerve Cell Pentraxin Proteins May Be New Biomarkers in Parkinson’s

Protein levels in CSF linked to worse motor, cognitive symptoms

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Levels of nerve cell pentraxin proteins found in the cerebrospinal fluid (CSF) surrounding the brain and spinal cord are associated with motor and cognitive decline in people with Parkinson’s disease and related conditions, a study suggests.

As such, these nerve pentraxins may serve as predictive biomarkers for both cognitive and motor symptom progression in Parkinson’s, the researchers said.

“Based on the associations between pentraxin levels and symptoms found in the present paper, they do seem to be potential monitoring biomarkers of disease severity, progression, and decline in parkinsonian disorders, in both motor and cognitive domains,” the team wrote.

The study, “Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction Are Altered in Parkinson’s Disease and Related Disorders,” led by researchers in Sweden, was published in the journal Movement Disorders.

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CSF Biomarkers May Distinguish Parkinson’s, Atypical Parkinsonism

Examining pentraxin proteins in Parkinson’s

In Parkinson’s, the toxic clumping of alpha-synuclein protein leads to the death of dopaminergic neurons, the specialized nerve cells that produce dopamine, a chemical signaling molecule, or neurotransmitter. The resulting lack of dopamine gives rise to Parkinson’s symptoms.

Synapses are the junctions between neurons where neurotransmitters like dopamine are released to facilitate cell-to-cell communication. Because alpha-synuclein is known to play a role in synaptic function in healthy brains, synaptic dysfunction is thought to precede nerve cell loss in related neurodegenerative disorders.

“The study of synaptic proteins is … of importance to find synaptic dysfunction biomarkers to improve diagnostic and prognostic assessment, especially in the early disease phase, and for monitoring treatment responses in future drug trials,” the researchers wrote.

To explore potential biomarkers of synaptic dysfunction in Parkinson’s, the team measured the levels of 15 synaptic proteins in the CSF collected from 51 adults with the neurodegenerative disease.

As a comparison, patients with conditions that have Parkinson’s-like features, referred to as atypical parkinsonism, also were enrolled. This group included 31 people diagnosed with multiple system atrophy (MSA), 22 with progressive supranuclear palsy (PSP), and 11 with corticobasal degeneration (CBD). A group of 48 healthy participants was included as controls.

CSF analysis revealed the level of the synaptic protein NPTX2, part of the neuronal pentraxin family (NPT), was significantly lower in people with Parkinson’s compared with controls — a result also found in those with CBD.

Among MSA and PSP patients, neurogranin synaptic protein and all three pentraxins — called NPTX1, NPTX2, and NPTXR — were present at significantly lower levels compared with the healthy group.

To confirm these findings, CSF samples from a second group of patients were assessed. This group included 95 individuals diagnosed with Parkinson’s, 26 with MSA, 22 with PSP, and three with CBD. A group of 23 adults with Alzheimer’s disease also was tested to determine whether the CSF profiles in Parkinson’s-related conditions differed from Alzheimer’s, according to the researchers.

Similarly, NPTX2 and NPTXR levels were significantly lower in Parkinson’s, MSA, and PSP patients, compared with controls. Low NPTX2 and NPTXR also were found in the Alzheimer’s group, while low NPTX1 was only seen in samples from PSP patients.

Higher CSF neurogranin levels were found in Alzheimer’s patients versus those with Parkinson’s, PSP, and MSA. A similar patternalso was observed for the proteins beta- and gamma-synuclein and 14-3-3 zeta/delta. No correlation between the use of Parkinon’s-related medications and synaptic protein levels was observed.Statistical analysis found NPTX2 levels best discriminated between patients with parkinsonism from controls and Alzheimer’s patients, whereas 14-3-3 zeta/delta levels best discriminated between parkinsonian patients and Alzheimer’s patients.

“Pentraxins do not seem to be useful as differential diagnostic biomarkers, as alterations were not found to be disease-specific,” the team wrote.

Because impaired synaptic function has been linked with neurodegenerative progression and cognitive decline, the team investigated a potential relationship between CSF pentraxins in Parkinson’s patients and clinical measures.

Significantly lower NPTX2 concentrations at baseline, the initial measurement, correlated with lower cognitive assessment scores in areas of visuospatial perception, language, executive function, working memory, and attention.

Lower NPTX2 levels also were associated with worse cognitive function at baseline, as measured by Mini-Mental State Exam (MMSE). Interestingly, higher levels of NPTX1, NPTX2, and NPTXR were associated with higher tremor scores.

Pentraxins … show promise to depict disease severity and track both motor and cognitive symptoms of [Parkinson’s]

Finally, lower baseline levels of all three pentraxin proteins were associated with faster Parkinson’s disease progression, as assessed by the postural imbalance and gait difficulty (PIGD) scores. Also, lower NPTX2 at baseline was associated with MMSE cognitive decline over time. However, progressive tremor scores were not related to pentraxin levels.

“Therefore, lower pentraxin levels seem to be correlated with both motor and cognitive disease severity in [Parkinson’s disease], and specifically with non-tremor symptoms,” the researchers wrote.

“These synaptic proteins should be further investigated to provide additional insights into the complex impacts different neuropathologies have on synaptic function,” they added.

The scientists concluded that the pentraxin proteins “show promise to depict disease severity and track both motor and cognitive symptoms of [Parkinson’s].”

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