AAN 2024 | Quantifying alpha-synuclein in the skin for the diagnosis of DLB: insights from Synuclein-One

This is a very exciting development where we’re looking at patients with dementia with Lewy bodies, using our skin biopsy test. This trial included 67 patients with dementia with Lewy bodies and 151 controls. We included an expert panel review in the study, so a group of highly trained neurologists specialized in this reviewed each case to determine whether they thought that true dementia with Lewy bodies was present or not. It turned out 50 of the 67 were approved by the expert panel to have a clinical diagnosis of dementia with Lewy bodies. In that population, the skin test identified 48 out of 50 to be positive, or 96%.

We also had 151 controls to help us identify what might be our false positive rate. The expert panel also reviewed them to see if they were truly healthy, and it turns out that 26 of them had what we call mild cognitive impairment, just spontaneously or de novo. These people didn’t know they were having cognitive issues, but they did on formal testing. Of that 26 group, 8 of the 26 had this protein deposited in their skin. So just over 30% of de novo diagnosis of mild cognitive impairment had this misfolded protein. Then, of 120 controls who were truly healthy, we actually had only 4 with this protein. So, 3.3% was what we consider the false positive rate. We dug into those 4 much more closely. Three of the four actually had subtle features to suggest they might actually have an underlying disease as well.

So, we feel that at the end of this study, it was a very sensitive and specific test for dementia with Lewy bodies. It really helps to identify that even at the mild cognitive impairment stage, so we may be able to detect this protein early. Ultimately, we do need to consider who the people with mild cognitive impairment are and who has this protein? Does it mean they’re going to develop DLB in the future? Unfortunately, we don’t know that yet, but that’s something that’s really important to follow.

The Synuclein-One study was actually the overarching study for which I was just referring to; this DLB was the first subgroup analysis of this. So, the Synuclein-One study actually included patients with Parkinson’s disease, multiple system atrophy, DLB, and pure autonomic failure. Each of these subgroups were analyzed separately. As we looked at these four subgroups of parkinsonism or synucleinopathies in this study, we found that the skin biopsies were on average, over 95% sensitive and over 95% specific for the diagnosis, confirming that skin can be a very efficient and effective way to help confirm a diagnosis of synucleinopathy.