Study Rationale: The Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) has amassed a comprehensive collection of samples and longitudinal clinicopathological data. In this project, we will take advantage of this resource to test cerebrospinal fluid (CSF) samples for alpha-synuclein using Amprion’s synuclein seed amplification assay (synSAA) and CSF and plasma samples for biomarkers of Alzheimer’s disease (AD), including amyloid beta plaques and phosphorylated tau protein tangles (using FDA-approved Roche Elecsys assays for the latter). The results of these assays will allow us to better classify subjects based on their disease pathology.
Hypothesis: We hypothesize that obtaining concurrent biomarker results for both Lewy body disease and Alzheimer’s disease will provide more informative classifications of subjects with Parkinson’s disease (PD) and dementia with Lewy bodies.
Study Design: We will test existing CSF and plasma biofluids inventory at AZSAND for alpha-synuclein and for AD biomarkers amyloid beta (plaques) and phosphorylated tau protein (tangles). We will use the results to classify and cross-reference Lewy body disease and healthy control subjects according to criteria from both the International Dementia with Lewy Bodies Consortium and the Neuronal Synuclein Disease – Integrative Staging System.
Impact on Diagnosis/Treatment of Parkinson’s disease: The concurrent staging of individuals for both Lewy body-synuclein and AD brain pathology will facilitate preclinical detection of Lewy body disease as well as improved prediction of clinical cognitive and motor decline.
Next Steps for Development: Clinical application of our study results would lead to consensus recommendations that all subjects entered into clinical trials for Lewy body disorders, whether for PD or for dementia with Lewy bodies, be classified into subgroups based on their combined tests for alpha-synuclein and AD biomarkers.