Blood Vesicles May Help ID Atypical Parkinsonism vs Parkinson’s

Vesicles found to help distinguish diseases with similar symptoms

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A dropper squirts out droplets of blood alongside several vials of blood.

Blood levels of neuron-derived small vesicles containing alpha-synuclein and tau protein clumps — both linked to neurodegenerative disorders — can accurately distinguish between people with Parkinson’s disease and those with atypical parkinsonism, a study found.

When isolated from the blood, these nerve cell vesicles may “provide a window into the brain’s biochemistry,” the researchers wrote.

For patients, they potentially can help distinguish Parkinson’s from other diseases with similar symptoms.

The study, “Oligomeric α-synuclein and tau aggregates in NDEVs differentiate Parkinson’s disease from atypical parkinsonisms,” was published in the journal Neurobiology of Disease.

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Parkinson’s, atypical parkinsonism can have same symptoms

Getting a diagnosis of Parkinson’s can take time because not all symptoms may be identified by conventional tests run in the doctor’s office. The diagnosis can be even harder when symptoms overlap with other neurodegenerative diseases that present as atypical parkinsonism, such as cortical basal degeneration (CBD) and progressive supranuclear palsy, known as PSP.

Atypical parkinsonism shows up as muscle tremors and stiffness, but is caused by different disorders than Parkinson’s.

As such, there is an urgent need for biomarkers in tissues and/or bodily fluids that may help discriminate between these similar conditions, and thereby reduce delayed diagnosis and misdiagnosis.

A previous study showed that levels of certain proteins including alpha-synuclein in the cerebrospinal fluid (CSF), which surrounds the brain and the spinal cord, could help discriminate Parkinson’s from atypical parkinsonism. However, CSF collection is a highly invasive procedure.

“In recent years the possibility of using neural-derived extracellular vesicles (NDEVs) as a ‘window’ into the brain has been suggested,” the researchers wrote.

NDEVs are tiny molecule-filled vesicles released by neurons or nerve cells and involved in cell communication. They are “readily accessible, as they can be isolated from blood and analyzed in their content of disease-associated molecules,” the researchers wrote.

To learn more, the team, based in Italy, tested how well blood levels of NDEVs containing alpha-synuclein clumps or tau protein aggregates could help tell Parkinson’s from atypical parkinsonism.

Toxic accumulation of alpha-synuclein clumps are a hallmark and driver of Parkinson’s disease. Toxic tau protein aggregates are mainly associated with Alzheimer’s disease, the leading cause of dementia, but also are found in people with Parkinson’s.

Blood samples were collected from 110 people: 70 with Parkinson’s (mean age, 69.5 years), 21 with PSP (mean age, 72.8 years), and 19 with CBD (mean age, 71.9 years). Participants were recruited from three Italian centers between September 2020 and December 2021.

On average, the Parkinson’s patients had been living with the disease for about three years longer than those with PSP or CBD. They also scored a mean of about seven to eight points higher on the Montreal Cognitive Assessment (MoCA), a measure of cognitive function in which higher scores indicate better performance.

The mean levodopa equivalent daily dose (LEDD) — the combined total of Parkinson’s medications — in Parkinson’s patients was about 2.4 times as high as in those with PSP and about 3.4 times as high as in those with CBD.

Results showed that NDEVs from the blood of people with Parkinson’s were found at numbers and sizes similar to those of PSP and CBD patients.

However, NDEVS from Parkinson’s patients contained in excess of seven times more alpha-synuclein clumps than those of people with atypical parkinsonism (1.69 vs. 0.22 nanograms per milliliter; a significant difference).

In turn, tau clumps were present in significantly higher amounts in NDEVs isolated from the blood of people with atypical parkinsonism relative to those with Parkinson’s (10.27 vs. 4.94 picograms per milliliter).

Levels of both alpha-synuclein and tau clumps in NDEVs were found to “have an ‘excellent’ power of classification” between Parkinson’s and atypical parkinsonism, the team wrote.

A minimally invasive blood test measuring the concentration of [alpha-synuclein] and tau aggregates … can represent a promising tool

Alpha-synuclein clumps showed a sensitivity of 78.6% (true-positive rate) and a specificity of 77.5% (true-negative rate), while tau aggregates had a 90% sensitivity and 75.7% specificity. A combination of both biomarkers resulted in 94.3% sensitivity and 67.5% specificity.

Levels of alpha-synuclein clumps worked best to distinguish Parkinson’s from CBD, with 88.2% sensitivity and 74.3% specificity. Those of tau clumps worked best to distinguish Parkinson’s from PSP, with 100% sensitivity and 75.7% specificity.

In addition, in the group of Parkinson’s patients,  higher levels of alpha-synuclein clumps were significantly associated with longer disease duration, worse motor symptoms, and higher LEDD. At the same time, higher levels of tau clumps were significantly linked to lower MoCA scores, indicating poorer cognitive function.

These findings highlight that alpha-synuclein and tau aggregates “have a promising potential to become disease-specific biomarkers in the clinical settings,” the researchers wrote.

“A minimally invasive blood test measuring the concentration of [alpha-synuclein] and tau aggregates in NDEVs can represent a promising tool to distinguish with high sensitivity and specificity [Parkinson’s disease] from CBD or PSP patients,” they added.

However, larger studies are needed to confirm these findings, the team noted.

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