So we are starting to move towards the biological definition of Lewy body disease. This is a concept that is now extended from Alzheimer’s disease which has the amyloid, tau, and neurodegenerative ATN criteria and now we are extending that to Lewy body disease where at least two different classification systems, one is a staging system, one is a classification system, not going to go into the two different types, but we’re really starting to look at how are these classification systems applying to our clinically diagnosed patients...
So we are starting to move towards the biological definition of Lewy body disease. This is a concept that is now extended from Alzheimer’s disease which has the amyloid, tau, and neurodegenerative ATN criteria and now we are extending that to Lewy body disease where at least two different classification systems, one is a staging system, one is a classification system, not going to go into the two different types, but we’re really starting to look at how are these classification systems applying to our clinically diagnosed patients. One of the things that there is a gap about is using an autopsy-validated cohort to look for, to validate some of these classification systems, particularly the Synergy classification, which looks at syn for alpha-synuclein, neurodegeneration, and genetics. And this is for Parkinsonism and all related disorders. So what we did was we looked at an autopsy-validated cohort, which had alpha-synuclein at pathology, and then we had CSF at postmortem that confirmed that pathology in CSF by alpha-synuclein seeding assays, which is one of our newer tests. We then also tried to find an autopsy definition of neurodegeneration, and in our cohort we do that using substantia nigra neuron loss. Now the Synergy Classification System typically thinks about that scan as that reference point, but in our case we’re looking at the autopsy cohort and we have decided that it may be more sensitive to look at autopsy neurodegeneration and we’re trying to see where do the different spectrums of Lewy body disease classify, so what we did find was the incidental Lewy body diseases and the Alzheimer’s disease with Lewy body diseases had synuclein positivity and neurodegenerative positivity and synuclein positivity and neurodegenerative negativity. So S plus and plus and S plus and minus cohorts, somewhat in similar ranges or more of a mixed range. And then the DLB and PD folks were primarily S plus and N plus. So they were, once they got to autopsy, they were showing both synuclein positivity and neurodegenerative positivity. What we also found that because we do a graded scale for our neurodegeneration, the stricter we got with our neurodegenerative processes, PD and DLB for the most part continued to be N positive, but the incidental Lewy body diseases and the Alzheimer’s disease with mixed Lewy body diseases were actually becoming more N negative in that gradient. What that tells us is that when you think about incidental transitional Lewy body disease, neurodegeneration may not be apparent if you don’t have a test that’s very sensitive. So depending on how that scan correlates with true neurodegeneration, we may not be able to detect neurodegeneration or classify these conditions as neurodegenerative diseases or having neurodegeneration in that process and how that really changes the conceptualization of the classification systems. So that’s the goal for this abstract.
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