Saliva is a promising fluid for biomarker discovery in PD and alpha-synuclein an obvious choice in terms of potential markers to investigate, because (1) we know it is a protein involved in the disease process, (2) we know synuclein inclusions occur in the salivary glands and (3) because it has shown potential as a biomarker in other fluids such as CSF.
It is really interesting that this group have chosen to look separately at a-syn monomers and oligomers (and not just total a-syn). Their finding of an increase in a-syn oligomers but a decrease in total a-syn reflects similar findings (an increase in oligomers but decrease in total a-syn) in CSF.
Personally, I also wonder whether their assays for a-synuclein might not be particularly accurate - I had difficulty detecting a-synuclein in saliva myself! They measure concentrations of oligomeric a-syn which are orders of magnitude higher than the total a-syn (which doesn't make sense) and also orders of magnitude different from the values for salivary a-syn reported in other studies.
It is really interesting that this group have chosen to look separately at a-syn monomers and oligomers (and not just total a-syn). Their finding of an increase in a-syn oligomers but a decrease in total a-syn reflects similar findings (an increase in oligomers but decrease in total a-syn) in CSF.
Personally, I also wonder whether their assays for a-synuclein might not be particularly accurate - I had difficulty detecting a-synuclein in saliva myself! They measure concentrations of oligomeric a-syn which are orders of magnitude higher than the total a-syn (which doesn't make sense) and also orders of magnitude different from the values for salivary a-syn reported in other studies.
PLoS One. 2016 Mar 24;11(3):e0151156. doi: 10.1371/journal.pone.0151156. eCollection 2016.
Giorgio Vivacqua , Anna Latorre , Antonio Suppa , Michela Nardi , Sara Pietracupa , Romina Mancinelli , Giovanni Fabbrini , Carlo Colosimo , Eugenio Gaudio , Alfredo Berardelli
ABSTRACT:
In Parkinson’s disease (PD), alpha-synuclein (a-syn) can be detected in biological fluids including saliva. Although previous studies found reduced a-syn total (a-syntotal) concentration in saliva of PD patients, no studies have previously examined salivary a-syn oligomers (a-synolig) concentrations or assessed the correlation between salivary a-syntotal, a-synolig and clinical features in a large cohort of PD patients. Is well known that a-synolig exerts a crucial neurotoxic effect in PD. We collected salivary samples from 60 PD patients and 40 age- and sex-comparable healthy subjects. PD was diagnosed according to the United Kingdom Brain Bank Criteria. Samples of saliva were analyzed by specific anti-a-syn and anti-oligomeric a-syn ELISA kits. A complete clinical evaluation of each patient was performed using MDS-Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Montreal Cognitive Assessment and Frontal Assessment Battery. Salivary a-syntotal was lower, whereas a-synolig was higher in PD patients than healthy subjects. The a-synolig/a-syntotal ratio was also higher in patients than in healthy subjects. Salivary a-syntotal concentration negatively correlated with that of a-synolig and correlated with several patients’ clinical features. In PD, decreased salivary concentration of a-syntotal may reflect the reduction of a-syn monomers (a-synmon), as well as the formation of insoluble intracellular inclusions and soluble oligomers. The combined detection of a-syntotal and a-synolig in the saliva might help the early diagnosis of PD.
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