The overall goal of our project is to validate a diagnostic tool for dementia with Lewy bodies (DLB), and Parkinson?s disease dementia (PDD), two common neurodegenerative diseases affecting 1.4 million people in the U.S. Currently, definitive diagnosis of DLB and PDD often requires the postmortem detection of disease- associated alpha-synuclein (?SynD) aggregates in the brain. Clinically, DLB and PDD can be easily misdiagnosed with other dementias and parkinsonisms such as Alzheimer?s disease (AD) and tauopathies. An unmet medical need is to identify biomarkers for early and differential diagnosis of DLB and PDD in more easily accessible tissues. We have taken advantage of the emerging technology known as the real-time quaking induced conversion (RT-QuIC) assay to develop a robust platform for ultrasensitive detection of ?SynD in peripheral tissues. In preliminary studies, we are able to detect prion-like seeding activity of ?SynD in the skin of DLB and PD patients with 100% specificity and sensitivity. In addition, we were remarkably successful in detecting ?SynD seeding activity in multiple peripheral tissues including skin, sigmoid colon, and submandibular glands in autopsied specimens. We hypothesize that RT-QuIC of peripheral ?SynD is a highly sensitive and robust diagnostic biomarker for premortem diagnoses of DLB and PDD. To test this hypothesis, we propose to pursue the following four Aims: (1) Establish peripheral ?SynD as a biomarker for postmortem diagnosis of DLB and PDD using RT-QuIC assay; (2) Assess skin ?SynD as a biomarker for premortem diagnosis of DLB and PDD; (3) Determine peripheral ?SynD and tau as a biomarker for differentiating DLB and PDD from other dementias and parkinsonisms such as AD and tauopathies; (4) Explore gut ?SynD as a biomarker for premortem diagnosis of DLB and PDD using colon biopsy. Successful implementation of this proposal will establish RT- QuIC assay utilization for early diagnosis of DLB and PDD using readily available peripheral specimens.
The overall goal of our project is to validate a diagnostic tool for dementia with Lewy bodies, and Parkinson?s disease dementia, two common neurological diseases currently affecting 1.4 million people in the U.S. Our study may ultimately help early diagnosis to improve patient care and aid the development of therapeutics for patients living with dementia with Lewy bodies and Parkinson?s disease dementia.
