So mild cognitive impairment is important because many patients will have, ultimately, either Alzheimer’s disease or dementia with Lewy bodies, kind of as the two most common forms of neurodegenerative disease that leads to dementia. Now, in both of those cases, there’s a very high prevalence of co-pathology that exists. And so this particular study is looking longitudinally at patients with mild cognitive impairment who have either a phenotype suggestive of Alzheimer’s or of dementia with Lewy bodies...
So mild cognitive impairment is important because many patients will have, ultimately, either Alzheimer’s disease or dementia with Lewy bodies, kind of as the two most common forms of neurodegenerative disease that leads to dementia. Now, in both of those cases, there’s a very high prevalence of co-pathology that exists. And so this particular study is looking longitudinally at patients with mild cognitive impairment who have either a phenotype suggestive of Alzheimer’s or of dementia with Lewy bodies. And we’re doing skin biopsies to look for phosphorylated alpha-synuclein, but we’re also doing blood-based biomarkers for ptau217 to look for dementia risk there. And we’re really characterizing both cohorts to see whether one biomarker or kind of dual pathology biomarker actually indicates a more rapid disease progression. So the first thing we found is that those with mild cognitive impairment that appear to have DLB, already 80% of them will have phosphorylated alpha-synuclein in the periphery. Interestingly, almost 40% of the patients with Alzheimer’s disease will also have peripheral alpha-synuclein. And when we follow over 12 months, those with suspected DLB have a very great increase in phosphorylated alpha-synuclein, so almost 40%, whereas those with Alzheimer’s have very little change. It’s still there, it’s just not changing to a significant degree. Now, what’s important about that data is those with both biomarkers, ptau217 and phosphorylated alpha-synuclein, have a more rapid cognitive decline. So if we look at something called the CDR, the Clinical Dementia Rating Scale, the sum of boxes is the score, those with both biomarkers will progress more rapidly over 12 months. This is the first time, I believe, in vivo that’s been seen. We know that from autopsy data, but this now really confirms that what we see at autopsy can be seen in life, even at the mild cognitive impairment stage.
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