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Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease
Ethan G Brown1, Lana M Chahine2, Andrew Siderowf3
1Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Annals of Neurology
|December 25, 2024
Summary
Remote smell testing and dopamine transporter imaging effectively identify individuals with alpha-synuclein aggregation. This approach aids recruitment for clinical trials targeting neurodegenerative diseases.
Area of Science:
- Neurology
- Biomarker Discovery
- Neuroimaging
Background:
- Remote identification of individuals with severe hyposmia (reduced sense of smell) is crucial for recruiting participants with alpha-synuclein aggregation.
- Alpha-synuclein aggregation is a key pathological hallmark in neurodegenerative diseases like Parkinson's disease.
Purpose of the Study:
- To evaluate a staged screening paradigm using remote smell testing to identify individuals with abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.
- To assess the performance of remote smell identification test (UPSIT) in enriching for participants with potential underlying neurodegenerative pathology.
Main Methods:
- The study utilized data from the Parkinson's Progression Markers Initiative (PPMI) prodromal cohort (age 60+).
- Participants completed an online University of Pennsylvania Smell Identification Test (UPSIT); those with hyposmia were invited for DAT-SPECT.
- Eligibility for further biomarker evaluation, including cerebrospinal fluid alpha-synuclein seed amplification assay (aSynSAA), was determined by DAT-SPECT results.
Main Results:
- Out of 31,293 UPSIT completers, 8,301 (27%) had scores indicating hyposmia (<15th percentile).
- Of 1,546 who underwent DAT-SPECT, 1,060 (69%) showed reduced dopamine transporter binding.
- Participants with severe hyposmia (UPSIT <10th percentile) were significantly more likely to have reduced DAT-SPECT binding (OR, 3.01).
- A high proportion (55-70%) of individuals with hyposmia and reduced DAT-SPECT binding tested positive for alpha-synuclein aggregation (aSynSAA).
Conclusions:
- Remote screening for hyposmia combined with DAT-SPECT effectively identifies individuals with a high likelihood of positive alpha-synuclein aggregation.
- This strategy can facilitate the recruitment of suitable participants for clinical trials.
- Longitudinal data are needed to understand progression patterns and inform recruitment for disease-modifying therapies.
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