Dementia with Lewy Bodies (DLB) is the second most common form of neurodegenerative dementia, however it is underrecognized and frequently misdiagnosed. Differently from Alzheimer's disease (AD), direct biomarkers specific to DLB pathology are not yet available for clinical diagnosis. DLB pathology is characterized by Lewy bodies at autopsy, consisting of abnormal aggregates of alpha-synuclein. Alpha-synuclein detection is one of the potential cerebrospinal fluid (CSF) biomarkers for DLB, however, findings from different studies are not conclusive. Lewy body pathology has been also found in submandibular glands in patients with Lewy body disease (LBD) and salivary alpha-synuclein has been detected in patients with Parkinson's disease. In this project we aim at investigating salivary alpha-synuclein total and oligomeric levels in DLB patients compared to Healthy controls (HC), to assess whether salivary alpha-synuclein can be used to differentiate DLB patients from HC. Specifically, we propose to perform the first two phases of the biomarker validation process. First, we will test whether salivary alpha-synuclein levels in DLB patients differ from those in HC and second, we will assess the accuracy of alpha-synuclein salivary test in detecting DLB, defining its sensitivity, specificity, positive and negative predictive values. We also aim at investigating whether salivary alpha-synuclein can differentiate DLB from AD and we will explore possible correlations between the DLB core features and salivary alpha-synuclein levels.
Hopefully, the results of the present project may provide evidence that salivary alpha-synuclein is a possible and easy testing biomarker and will open new opportunities for DLB diagnostic biomarkers.
The lack of biomarkers related to DLB diagnosis makes challenging recognizing this form of dementia in clinical settings. Although it is the second most common cause of dementia it is still underrecognized and there are no available disease modifying treatment for this form of dementia.
a-synuclein is the pathological hallmark of this form of dementia but there are no validated procedures to assess this biomarker in vivo. Saliva is a biological fluid easy to collect which may contain a- synuclein in DLB.
The detection of salivary a- synuclein might be a promising biomarker and no previous studies have investigated a- synuclein in DLB patients.
The process to validate a biomarker is a multistep process aimed at assessing analytical validity (i.e., accuracy, reliability, and reproducibility), clinical validity (i.e., how well the test measures the clinical features, and the disease or treatment outcomes) and clinical utility (i.e., if and how the test improves the patient's outcomes, confirms/changes the diagnosis, identifies at-risk individuals, influences therapeutic choices).
The first phase of the validation process assesses whether the test results in patients with the target disease differ from those in normal controls. The second phase assesses the accuracy of the test in distinguishing patients with the disease from normal controls (Canevelli et al., 2019).
Here we propose to perform the first 2 phases of the biomarker validation process. First we will test whether salivary a-synuclein levels in DLB patients differ from those in HC and second we will test the accuracy of a-synuclein salivary test in distinguishing DLB patients from HC, assessing its sensitivity, specificity, positive and negative predictive values.
We will also explore whether differences exist in salivary a- synuclein levels between AD and DLB and whether the test might a valid tool in differentiating these forms of dementia.
Moreover we will explore whether salivary a-synuclein levels are associated with DLB clinical features.
Overall, the results of the present project might provide evidence that salivary a-synuclein is a possible, easy testing, biomarker and will open new opportunities for DLB diagnostic biomarkers and hopefully for the preparation of clinical trial ready cohort for new therapeutic strategies.