D'Antonio Fabrizia, Vivacqua Giorgio, Serrentino Marco, Nalepa Martyna, Skweres Aleksandra, Peconi Martina, De Bartolo Maria Ilenia, Panigutti Massimiliano, Sepe Monti Micaela, Talarico Giuseppina, Fabbrini Giovanni, Bruno Giuseppe
Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
Cognitive and Motor Rehabilitation and Neuroimaging Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
J Alzheimers Dis. 2025 Mar;104(2):452-462. doi: 10.1177/13872877251317720. Epub 2025 Mar 14.
BackgroundDespite 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.ObjectiveThis 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).MethodsWe 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.ResultsSalivary 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.ConclusionsThese 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.
背景
尽管路易体痴呆（DLB）是神经退行性痴呆的第二常见形式，但超过80%的DLB病例最初被误诊。α-突触核蛋白（α-syn）和tau蛋白已在DLB患者的外周组织和生物体液中被检测到，在不同的生物体液中，唾液是一种易于获取且非侵入性的生物标志物检测来源。
目的
本研究旨在调查唾液中的α-syn和tau蛋白作为分子疾病生物标志物，评估它们在DLB诊断以及与阿尔茨海默病（AD）和帕金森病（PD）的鉴别诊断中的潜力。
方法
我们使用定量酶联免疫吸附测定（ELISA）分析，测量了21例DLB患者、20例AD患者、20例PD患者和20名健康受试者（HS）唾液中的总α-syn和寡聚α-syn、总tau蛋白以及S199磷酸化tau蛋白（pS199-tau）。
结果
不同组之间唾液总α-syn没有显著变化，而所有病理组的寡聚α-syn浓度均高于HS。所有病理组的唾液总tau蛋白浓度均高于HS，而患者组之间的浓度没有差异。相反，DLB和AD患者的唾液pS199-tau水平高于HS和PD患者。相关矩阵和主成分分析均显示，DLB的核心临床特征与α-syn病理相关，而认知下降与DLB和AD患者唾液中的pS199-tau水平相关。受试者操作特征分析表明，α-syn寡聚体和pS199-tau在DLB和HS之间具有较高的诊断准确性，在DLB和PD之间具有足够的准确性。相反，DLB患者和AD患者之间的诊断准确性并不理想。
结论
这些发现提供了初步证据，表明唾液中的α-syn和tau蛋白在鉴别DLB患者与PD患者和HS方面可能具有前景，而在与AD的鉴别诊断方面，其诊断潜力有限。
