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Lack of Standardized Vitamin D Data Hampers Efforts to Determine Its Role in Parkinson’s, Review Study Says

Vitamin D, Parkinson's risk

Low vitamin D serum levels have been associated with Parkinson’s disease, but the lack of standardized data makes it difficult to determine vitamin D’s exact role in Parkinson’s pathology, according to a recent review article.

The study, “Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer’s disease and Parkinson’s disease,” was published in Clinica Chimica Acta.

Vitamin D is essential to maintain homeostasis of the musculoskeletal system, and exists in two forms: 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. The major form found in the blood is 25-hydroxyvitamin D, and as such, testing usually quantifies these levels to monitor vitamin D status in individuals.

Low serum vitamin D levels have been associated with Parkinson’s disease, suggesting that elevated vitamin D levels could protect against this neurodegenerative disorder.

In 2010, researchers analyzed the blood concentrations of vitamin D in 3,173 men and women, 50–79 years old, and found that those with higher levels were less likely to develop Parkinson’s. Standardized techniques were used to measure these levels, which revealed that 50 out of the 3,173 people developed Parkinson’s, which is a relatively small number for scientists to draw conclusions on the “protective power” of vitamin D.

In another study, 25-hydroxyvitamin D blood concentration was found to be significantly associated with motor severity in 145 Parkinson’s patients who were followed for three years. These findings were further supported by two recent meta-analyses evaluating a total of 4,199 patients. Results revealed that serum vitamin D levels were inversely associated with Parkinson’s risk and severity, and that vitamin D supplementation did not improve subjects’ motor function. However, the methods used to quantify vitamin D levels varied between the studies included in the combined statistical analyses.

In an attempt to standardize vitamin D measurements, researchers in the current study reviewed the performance of 25-hydroxyvitamin D assays over the last three decades. So far, “only a few studies evaluating relatively small samples reported standardized data,” the researchers wrote.

“Literature studies in the field of vitamin D mainly report unstandardized results, which hampers the development of consensus guidelines defining optimal vitamin D status,” they said, adding that current data do not support the usefulness of vitamin D as a biomarker for Parkinson’s disease and that further studies “using internationally recognized measurement procedures and materials are required.”

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Alpha-synuclein in Blood Serum May Be Early Parkinson’s Biomarker, Study Suggests

biomarker, alpha-synuclein

Measuring the amount of alpha-synuclein in tiny vesicles collected from blood serum may help diagnose early Parkinson’s and identify patients with different types of this disease.

The study with that finding, “Central Nervous System-Derived Exosomal Alpha-Synuclein in Serum May Be a Biomarker in Parkinson’s Disease,” was published recently in the journal Neuroscience.

As both resting and posture tremor may occur in the early stages of Parkinson’s, patients may be misdiagnosed with essential tremor. Similar to Parkinson’s, essential tremor is a progressive movement disorder, and it predominantly affects hands and arms.

Alpha-synuclein is the main component of Lewy bodies, characteristic protein aggregates that accumulate in brain cells of Parkinson’s patients.

Compared to unaffected individuals, Parkinson’s patients typically have lower levels of alpha-synuclein in their cerebrospinal fluid — the liquid surrounding the brain and spinal cord — which correlates with prognosis. However, measuring alpha-synuclein in the clinic has been precluded by the invasive nature of spinal tap and by the inconsistent results of plasma or serum samples.

Exosomes are tiny vesicles released by neurons and other cells, and have been implicated in the transmission of misfolded proteins, including alpha-synuclein in people with Parkinson’s. As such, researchers hypothesized that exosomes derived from the central nervous system (CNS) could be a peripheral biomarker of Parkinson’s disease.

The scientists recruited 38 newly diagnosed, untreated patients with early Parkinson’s divided into tremor-dominant (TD, 22 patients, mean age 62.7 years) and non-tremor-dominant (NTD, 16 patients, 62.1 years), who were compared to 21 patients with essential tremor (62 years) and 18 healthy controls.

Among the patients with Parkinson’s, those with TD had a shorter disease duration than the people with the NTD subtype (19.2 vs. 35.8 months). The age at disease onset did not differ in these two groups – 61.1 years in TD and 59.1 years in NTS patients.

The results revealed that Parkinson’s patients had lower levels of alpha-synuclein in CNS-derived serum exosomes than those with essential tremor or controls. Importantly, within Parkinson’s patients, those with the NTD type — which has been associated with more frequent depression, lack of motivation and impairment in activities of daily life — had lower amounts than those in the TD subset.

A subsequent analysis found that exosomal alpha-synuclein had a moderate potential to diagnose Parkinson’s disease and a great potential to diagnose non-tremor-dominant patients.

Of note, the amount of CNS-derived alpha-synuclein in exosomes was not significantly associated with disease duration or severity.

Overall, “CNS-derived exosomal [alpha]-synuclein in the serum may be regarded as a biomarker to identify [early Parkinson’s],” the scientists wrote.

Cautioning that studies with larger groups of patients and those with longitudinal monitoring are needed, the team further commented that assessing alpha-synuclein in serum exosomes also may help identify different Parkinson’s types.

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