Salivary biomarkers for the molecular diagnosis of dementia with Lewy bodies

Background: Despite dementia with Lewy bodies (DLB) being the second most common form of neurodegenerative dementia, more than 80% of DLB cases are initially misdiagnosed. Alpha-synuclein (a-syn) and tau species have been detected in peripheral tissues and biological fluids of DLB patients and among different biological fluids, saliva represent an easely accessible and non-invasive source for biomarker detection. Objective: This study aimed to investigate salivary a-syn and tau species as molecular disease biomarkers, assessing their potential in the diagnosis of DLB and in the differential diagnosis on respect to Alzheimer's disease (AD) and Parkinson's disease (PD). Methods We measured total and oligomeric a-syn, total-tau, and S199-phosphorylated-tau (pS199-tau) in the saliva of 21 DLB, 20 AD, 20 PD patients, and 20 healthy subjects (HS) using quantitative enzyme-linked immunosorbent assay (ELISA) analyses. ResultsL Salivary total a-syn was not significantly changed between the different groups, whereas all pathological groups had a higher oligomeric a-syn concentration than HS. Salivary total-tau concentration was higher in all the pathological groups than HS, whereas the concentrations did not differ among patients' groups. Conversely, salivary levels of pS199-tau was higher in DLB and AD patients than in HS and PD patients. Both correlation matrix and principal component analysis showed that core clinical DLB features were related to a-syn pathology, while cognitive decline was associated with salivary levels of pS199-tau in both DLB and AD patients. Receiver operating characteristic analysis reported high diagnostic accuracy for both a-syn oligomers and pS199-tau, between DLB and HS, and an adequate accuracy between DLB and PD. Conversely, the diagnostic accuracy was not optimal between DLB patients and AD patients. Conclusions LThese findings provide preliminary evidence that salivary a-syn and tau species might be promising in identifying DLB patients on respect to PD patients and HS, while the diagnostic potential is limited on respect to AD.