Alpha-synuclein saliva biomarker for Parkinson's not ready for prime time

2019 08 19 17 49 8154 Parkinsons Lewy Bodies 400

The level of the protein alpha-synuclein (α-Syn) in saliva has theoretical potential as an early, noninvasive diagnostic biomarker for Parkinson's disease, but there are still many uncertainties regarding its value and how it could be used in practice, according to a systematic review published online in the Journal of Neural Transmission.

Researchers at the University of Athens evaluated the use of salivary α-Syn as a diagnostic marker in eight trials including a total of 1,240 patients identified through a systematic review of 476 studies. They found different results depending on the way α-Syn was measured -- total α-Syn versus oligomeric salivary α-Syn.

The diagnostic performance of both tests -- total and oligomeric salivary α-Syn -- "is not yet at the level needed to justify their introduction into clinical practice," concluded lead author Anastasia Bougea, PhD, and colleagues (J Neural Transm, August 10, 2019).

Parkinson's biomarkers a 'high priority'

The literature review was conducted because a biomarker for early disease pathology in Parkinson's is a high research priority, and there have been promising results for salivary α-Syn, the authors noted. An accessible biomarker, such as one that can be measured in saliva, would be ideal.

Motor symptoms of Parkinson's tend to manifest after the destruction of dopaminergic neurons, which limits the treatment options for patients, they noted.

"Currently available therapies are unsatisfactory, inasmuch as they either stabilize or improve symptoms, or they decelerate the progression of symptoms, but they do not have an effect on the progression of the underlying neurodegenerative mechanisms," Bougea and colleagues wrote. "This fact highlights the need for the development of biological indicators to enable a timely and accurate diagnosis and the future implementation of neuroprotective therapies."

Among other biomarker options, α-Syn in the blood and cerebrospinal fluid has emerged as a leading candidate to help detect disease in earlier stages. However, results have been variable, due in part to differences in methodologies used in studies and the tests for evaluating α-Syn levels.

Mixed results for saliva tests

The review in the Journal of Neural Transmission showed mixed results for tests of the biomarker in saliva. For example, in three studies, total α-Syn levels were significantly lower in patients with Parkinson's disease than in healthy controls, but in the five other studies in the review, there was no significant association, the researchers reported. They associated α-Syn with clinical features in some studies, but "no consistent pattern emerged."

Whereas total α-Syn levels dropped in Parkinson's patients as they got older, salivary oligomeric α-Syn was higher in patients with the disease than in those without it. Bougea and colleagues found evidence in half of the studies that patients with Parkinson's had higher levels of salivary oligomeric α-Syn and a higher ratio of oligomeric α-Syn to total α-Syn, compared with healthy controls, but did not see the same evidence in the other studies. In addition, results for salivary α-Syn in the studies evaluated did not correlate with samples of blood and cerebrospinal fluid.

Differences in study conduct and methods likely influenced the results; for example, the populations were heterogenous, and practices in specimen handling and the way salivary testing was done varied. The sample sizes were small, and in most studies, genetic testing had not been done. An estimated 10% to 15% of Parkinson's disease cases are genetically based, and the Parkinson's Foundation is rolling out a free genetic testing program in partnership with Fulgent Genetics.

"Taken together, the potential of salivary total α-Syn as a [Parkinson's disease] biomarker is still uncertain, whereas salivary oligomeric α-Syn appears quite promising," Bougea and colleagues concluded. "[Preanalytical] and analytical factors of included studies were important limitations to justify the introduction of salivary α-Syn into clinical practice."

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