Promising Diagnostic Approaches Emerging for Brain Pathologies: James Leverenz, MD

WATCH TIME: 3 minutes

"I think a lot of people are starting to use these aggregate assays...it does help us give a more accurate diagnosis and at least manage some of the adverse effects of these diseases."

In prior studies, Synuclein Aggregate Assays (SAA) in cerebrospinal fluid (CSF) and skin biopsies have been effective in detecting underlying synuclein (Lewy body) pathology in Parkinson disease, yet data on their effectiveness in Lewy body dementia (LBD) is limited. However, a recent study utilizing data from the U.S.-based Dementia with Lewy Bodies Consortium (DLBC) presented at the 2024 Alzheimer’s Association International Conference, July 28 to August 1, in Philadelphia, Pennsylvania, demonstrated that CSF-based SAA testing was successful in identifying LBD with autopsy-confirmed limbic or neocortical stage Lewy body pathology (LBP).¹

The study, presented by lead author James Leverenz, MD, director of the Cleveland Lou Ruvo Center for Brain Health at Cleveland Clinic, investigated the performance of CSF-based SAA and Alzheimer disease biomarkers in relation to the post-mortem presence and staging of LBP and Alzheimer’s Disease Neuropathologic Change (ADNC) among DLBC participants. To date, 31 of these cases have undergone autopsy and were staged for LBP, ADNC, and TDP-43 pathology. The analysis also revealed that detection of LBP was less reliable when the pathology was confined to more limited anatomical regions, such as the brainstem or amygdala, and no false positives for CSF SAA were observed in this sample of LBD cases.

At the recently concluded conference, Leverenz sat down with NeurologyLive^® in an interview to discuss how the initial brain regions affected by pathology influence the progression of neurological diseases like Alzheimer and Lewy body diseases. During the conversation, he also talked about the current challenges in making advanced diagnostic assays more widely accessible in the general medical community. Moreover, Leverenz spoke about how the development of imaging ligands and blood-based diagnostics might change the future of neurological disease management.

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REFERENCES
1. Leverenz JB, Patel P, Bekris LM, et al. Synuclein Aggregate Assay Performance in Autopsy-Confirmed Lewy Body Dementia: Results from the U.S. Dementia with Lewy Bodies Consortium. Presented at: 2024 Alzheimer’s Association International Conference; July 18 to August 1; Philadelphia, Pennsylvania.